ARTICLE |
Correspondence to: Matti Korhonen, Dept of Anatomy, Inst. of Biomedicine, PO Box 9, FIN-00014 University of Helsinki, Finland.
![]() |
Summary |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
We studied the distribution of laminin (Ln) 1-
3, ß1-ß3, and
1 chains, and of the extradomain-A (EDA) and EDB and the oncofetal epitope of fibronectin (Onc-Fn) in extravillous trophoblastic cells and decidua in the human placenta by immunohistochemistry. We found that the transition from villous to extravillous trophoblast was accompanied by emergence of immunoreactivity for EDA-, EDB-, and Onc-Fn among the cells. Furthermore, whereas the villous trophoblastic basement membrane (BM) contains Ln
1,
2, ß1, ß2, and
1 chains, immunoreactivity for Ln
1, ß1, and
1, but not for Ln
2 and ß2 chains, was detected in association with extravillous trophoblastic cells. Interestingly, although immunoreactivity for the Ln
1,
2, ß1, ß2, and
1 chains was detected in all decidual cell BMs, EDB-Fn and Onc-Fn were detected only in decidua that had been invaded by the trophoblast. In summary, our results describe distinct changes in the distribution of Ln and Fn isoforms during the differentiation of villous trophoblast into extravillous trophoblastic cells. Furthermore, EDB- and Onc-Fn are preferentially found in decidua that has been invaded by the trophoblast, indicating that the deposition of these Fn isoforms reflects a decidual cell response to invasion. (J Histochem Cytochem 45:569-581, 1997)
Key Words: placenta, human, extravillous trophoblastic cells, decidual cells, laminin, fibronectin, immunohistochemistry, basement membrane, extracellular matrix
![]() |
Introduction |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The cyto- and syncytiotrophoblast form the epithelial covering of fetal chorionic villi. The villous cytotrophoblastic cells are capable of fusing to form syncytiotrophoblasts that comprise the outer cellular layer covering the villi. The extravillous trophoblastic cells (ETCs) represent another unique direction of cytotrophoblastic cell differentiation (
Laminins (Lns) are a family of extracellular matrix glycoproteins that are important basement membrane (BM) constituents. They are heterotrimers, consisting of an -, a ß-, and a
-type chain. Several isoforms have been described for each chain type (
Immunolocalization studies have revealed that Ln is found in villous BMs (
Recently, we found that the invasion of the uterine wall by the ETCs is accompanied by a change in integrin expression of the invading cells. When villous trophoblastic cells differentiate into ETCs in anchoring columns, the cells cease to express the integrin 6ß4, which is a Ln receptor, and begin to express the
1ß1 and
5ß1 integrins, which bind Ln and Fn, respectively (
![]() |
Materials and Methods |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Tissues
A total of 16 human placentas (seven 8-10 weeks, five 12-20 weeks, and four 38-40 weeks of gestation) were acquired from spontaneous abortions due to rupture of fetal membranes, from legal abortions performed for psychosocial indications, or from normal deliveries (Jorvi Hospital; Espoo, Finland). The tissues were frozen in liquid nitrogen and stored at -74C until use. Routine hematoxylin-eosin staining was used to establish the normal histology of the tissue samples.
Immunoprecipitation and Western Blotting
For SDS-PAGE and Western blotting, whole placental tissue was extracted in electrophoresis sample buffer (
Antibodies
MAbs and antisera to Lns and Fns were as follows: 1 (clone 4C7;
2 (clone 5H2;
3 (clone BM-2;
1 (clone 2E8;
The designation of the epitopes recognized by the various Fn antibodies requires comment. The MAbs 52DH1 and BC-1 used in this study recognize EDA- and EDB-Fns, respectively (
Immunohistochemistry
Frozen sections were cut at 5 µm and fixed in acetone at -20C for 10 min. For indirect immunofluorescence microscopy, the sections were exposed to the primary and subsequently to the secondary antibodies (fluorescein isothiocyanate-coupled goat anti-mouse IgG and tetramethylrhodamine-coupled goat anti-rabbit IgG sera; Jackson Immunoresearch, West Grove, PA) at room temperature (RT) for 30 min. For negative controls, sections were exposed only to the secondary antisera. The specimens were embedded in sodium veronal/glycerol buffer (1:1; pH 8.4) and examined with a Leitz Aristoplan microscope equipped with appropriate filters. For light microscopy, sections were exposed to the primary antibodies at RT for 30 min. The bound antibodies were visualized with the APAAP (alkaline phosphatase-anti-alkaline phosphatase) method (Dako). Endogenous alkaline phosphatase was blocked with 1 M levamisole (Sigma). Negative controls were carried out for each set of serial sections by omitting the primary antibodies. The controls revealed minor unspecific staining in certain areas of the tissue sections; these were excluded from the study. The sections were counterstained with Mayer's hematoxylin (Merck; Darmstadt, Germany) and mounted in GVA mounting medium (Zymed; San Francisco, CA).
Placental Histology and Nomenclature
The distribution of the various Ln and Fn isoforms was evaluated by indirect immunofluorescence as well as light microscopy from sets of serial sections of the placental samples. Histology of the immunofluorescence sections was evaluated by light microscopy of adjacent sections. We have used descriptive terms such as "weak" and "strong" to denote the intensity of the immunoreaction compared to other areas within the same microscopic section. Other terms such as "sparse" or "specks" vs "rich" or "extensive" immunoreactivity were used to describe the distribution of the immunoreactivity. Nomenclature for placental structures has been adopted from
![]() |
Results |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The immunolocalization results are summarized in Table 1.
|
Specificity of the ß2 MAb in Human Placental Tissue
MAb C4 recognizes the Ln ß2 chain in several species, including human. However, weak crossreactivity of the MAb with the Ln ß1 chain and an unidentified 400-kD protein has been reported in rat protein extracts. We used Western blotting of whole human second-trimester placental lysates and desoxycholate extracts of human placentas to define the specificity MAb C4 (Figure 1). These results demonstrate that it recognizes a single 190-kD band corresponding to the Ln ß2 chain but does not react with the ß1 chain or a higher molecular weight band in the human placenta.
|
ETCs in Cell Islands
Trophoblastic cell islands of the first trimester placenta are frequently cellular, with little extracellular material. Antibodies to Ln 1 (Figure 2c), ß1 (Figure 2a), and
1 chains revealed small specks of immunoreactivity in the midst of the trophoblastic cells, whereas no immunoreactivity for the Ln
2 (Figure 2e) or ß2 (Figure 2f) chains was seen. In double stainings, the polyclonal Ln antiserum reacted with the same specks as the anti-
1, -ß1 (Figure 2a and Figure 2b), and -
1 chain MAbs. Double immunostainings using anti-desmin (Figure 2c and Figure 2d) on -vimentin sera showed that no villous stromal cells were found within cell islands. Whereas the anti-Ln ß1 chain MAb revealed specks of immunoreactivity (Figure 3a), the MAbs recognizing the EDA- (Figure 3b), EDB- (Figure 3c), and Onc-Fn (Figure 3d) revealed rich immunoreactivity among the cells throughout the islands. Often, cell islands were associated with a villus via a trophoblastic cell column. Here, the nuclei of the trophoblastic cells most proximal to the villous BM (proliferative zone) reacted intensively with MAb Ki-67, a marker of proliferative cells (Figure 3e and Figure 3f). The first row of cells rested on the villous trophoblastic BM which was immunoreactive for the Ln
1,
2, ß1, ß2 and
1 chains. Otherwise, however, the first cell rows in the proliferative zone were devoid of Ln and Fn chain immunoreactivity (Figure 3a-f).
|
|
During the second and third trimesters of placental development, cell islands characteristically consist of ETCs embedded within fibrinoid material. Distinct Ln ß1 chain immunoreactivity, co-extensive with that seen with the polyclonal Ln antiserum, was detected among the fibrinoid material within the cell island (Figure 4a and Figure 4b). A similar, albeit less intensive, immunoreactivity was detected for the Ln 1 (Figure 4c and Figure 4d) and
1 chains, whereas the Ln
2 (Figure 4e and Figure 4f) and ß2 antibodies did not react with the fibrinoid material. As in cell islands without fibrinoid, abundant immunoreactivity for EDA-, EDB-, and Onc-Fns was detected within the fibrinoid (not shown).
|
ETCs in Anchoring Cell Columns
The Ln 1,
2, ß1, ß2 and
1 MAbs all reacted with the villous trophoblastic basement membranes at the villus-column interphase. The nuclei of the basal first to fifth rows of cells adjacent to the villous BM reacted intensively with the proliferation marker Ki-67 (proliferative zone; not shown). The Ln and Fn antibodies did not react with these most basal cell rows in the columns. In the proximal part of the matrix deposition zone, small specks of Ln
1, ß1 (Figure 5a and Figure 5b) and
1 chain immunoreactivity were seen. ETCs that were located more distally in the columns (matrix deposition zone) were surrounded by distinct linear Ln
1, ß1 (Figure 5a and Figure 5b) and
1 chain immunoreactivities, and extensive immunoreactivity for EDA-, EDB-, and Onc-Fns (Figure 5e and Figure 5f). The Ln
2 (Figure 5c and Figure 5d) and ß2 chains were not detected among ETCs in anchoring cell columns.
|
Double immunostainings using the polyclonal anti-cytokeratin serum enabled us to identify individual ETCs that had invaded further into the placental plate (invasion zone). These cells reacted heterogeneously with the Ln antibodies: a part of the cells were devoid of cell-associated Ln chain immunoreactivity, whereas some cells presented weak reactivity for the Ln 1 (Figure 6a and Figure 6b) ß1 and
1 chains. MAbs to the Ln
2 and ß2 chains reacted weakly at the surface of a small minority of the ETCs that were found among the decidual cells. Similarly, immunoreactivity for the Fn isoforms was variable, with some cells displaying distinct pericellular immunoreactivity whereas other cells appeared negative (Figure 6c and Figure 6d, displaying EDA-Fn). Only occasionally did these cells display nuclear positivity for MAb Ki-67 (not shown).
|
ETCs within the walls of spiral arteries reacted with MAbs to Ln 1 (Figure 6e and Figure 6f), ß1 and
1 chains, but not with MAbs to
2 (Figure 6g and Figure 6h) or ß2. MAbs against the Fn isoforms reacted distinctly with these ETCs (not shown).
Decidual Cells
MAbs to the Ln 1,
2 (Figure 7b), ß1 (Figure 7a), ß2 (Figure 7c) and
1 chains revealed linear pericellular immunoreactivity around the decidual cells. The immunoreactivity co-aligned with that of a polyclonal anti-Ln serum not shown), surrounding the individual cells in a basement membrane-like fashion.
|
Interesting differences regarding the distribution of Fns were noted in decidual tissue. In decidual tissue that was not invaded by ETCs, the MAb recognizing the EDA-Fn reacted only weakly and the MAbs to EDB-Fn (Figure 7e) and ONC-Fn (Figure 7f) did not react with decidual cell basement membranes. In samples in which invasion by ETCs was detected by double immunostaining with cytokeratin 19 antiserum, intensive immunoreactivity for EDA-, EDB-, and ONC-Fns (Figure 7i) was seen in decidual cell BMs and the intercellular matrix. One of the tissue samples from a 10-week placenta contained both areas with and areas without ETC invasion; the same differential distribution of Fn epitopes was detected in the two areas. In contrast to the differences in Fn distribution, the anti-Ln 2, ß1 (Figure 6d and Figure 6g), and ß2 MAbs reacted with decidual cell BMs in all decidual samples. The MAb recognizing Ln
1 reacted weakly but detectably with decidual tissue without ETC invasion, whereas more distinct (Figure 6a and Figure 6b) immunoreactivity was detected for this Ln chain in samples with invasion.
The Ln 3 and ß3 chains, components of Ln-5, Ln-6 and Ln-7, were not detected in ETCs or the decidua (not shown).
![]() |
Discussion |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The distribution of Ln and Fn isoforms in the extravillous trophoblast is significant in two respects. Altered expression of receptors for extracellular matrix components, including receptors for Lns and Fns, has been shown to accompany trophoblast detachment from the villous BM and subsequent invasion into the placental bed (
Although MAb C4 has been widely used to detect the Ln ß2 chain in tissue sections,
The MAb 4C7 does not recognize denatured laminin in Western blots, and its specificity has been shown indirectly. It binds to the G-domain of a Ln -type chain (
1 chain (
2 (
3-
5 chains are distinct from the heavy chain recognized by the MAb 4C7 (
1 chain, but confirmation of its epitope will require the characterization of other
1-specific antibodies. To our knowledge, no such MAbs are available at present.
Decidual Response to Invasion
Decidualization is accompanied by the deposition of a BM around each individual decidual cell. This BM has been shown to consist of Ln, Fn, Type IV collagen, and heparan sulfate proteoglycan (1,
2, ß1, ß2, and
1 chains. Interestingly, increased immunoreactivity for EDA-Fn and emergence of the EDB- and Onc-Fn epitopes were detected only in decidual tissue that was invaded by ETCs. These results suggest that deposition of these Fn epitopes in decidual cell BMs is a response to invasion by the ETC and is distinct from decidualization itself. Deposition of alternatively spliced Fn isoforms is likewise found in the stroma of malignant tumors (
2, ß1, ß2, and
1 chains are found in decidual cell BMs, but that only minor amounts of the
1 chain are present. In our samples, the immunoreaction for the
1 chain was indeed weak in decidual tissue without ETC invasion but was distinct around decidual cells of invaded tissue.
The Extracellular Matrix of Cell Islands and Columns
Trophoblastic cell islands of the first trimester (8-10 weeks in our material) were often cellular, with only a limited amount of extracellular material. On the other hand, some first-trimester and most of the second- and third-trimester cell islands consisted of ECTs enmeshed in fibrinoid material. The extracellular matrix in these structures has been termed "matrix-type fibrinoid" (1, ß1, and
1 chains (components of Ln-1), whereas the Ln
2 and ß2 chains were not detected. The matrix was also strongly immunoreactive for EDA-, EDB-, and Onc-Fn.
Recently, a gradient of Ln and Fn chain distribution along the proximal-distal axis of cell columns has been described (1, ß1,
1,
2, and ß2 chains found in the basement membrane. The first three to five cell layers were completely devoid of Ln and Fn chain immunoreactivity. Distinct nuclear reactivity for MAb Ki-67 identified these cells as a proliferating cell population (the proliferative zone). The cells located more distally in the columns were surrounded by distinct immunoreactivity for Ln
1, ß1, and
1 chains and for EDA-, EDB-, and Onc-Fns (matrix deposition zone).
In addition to the sites at which villi were anchored to the basal plate or placental septa, trophoblastic cell columns were also found at sites where a villus was located immediately adjacent to a cell island. In all these locations, the matrix molecule gradient described above was likewise found, and the most proximal cell rows of the columns contained Ki-67 antigen-positive nuclei as a sign of active cell proliferation. It has been proposed that cell islands and columns may be homologous structures (
Changes in the Extracellular Matrix Characterize ETC Differentiation
Our results suggest that all ETCs, found in diverse locations in the placenta such as in cell islands, cell columns of anchoring villi, the trophoblastic shell, as individual trophoblastic cells among the decidual cells within the basal plate, and as intra-arterial trophoblasts, are frequently associated with immunoreactivity for the Ln 1, ß1, and
1 chains, whereas the
2 and ß2 chains are not found. This is interesting in light of the finding that all of these chains are present in the villous trophoblastic BM. It would be interesting to determine whether the Ln
2 and ß2 chains are actually expressed in situ by villous trophoblastic cells and downregulated on ETC differentiation. Alternatively, these chains could be deposited into the villous BM solely by the villous stromal cells, as has been suggested for some BMs (
2 and ß2 chains that were sporadically found associated with ETCs found within the decidua could represent Lns that have been secreted by the neighboring decidual cells and assembled at the ETC surface. In partial contrast to our results,
2 chain in extravillous trophoblasts within the basal plate, using pepsin-digested paraffin sections. It should be emphasized that they reported cytoplasmic and not pericellular BM-like immunoreactivity for the Ln
2 chain. Our results, however, are supported by those of
2 chain in cell columns.
The distribution of Fn isoforms in ETCs is worth noting. Fn per se is found in the villous trophoblastic BM in the early developing placenta but disappears during the late first trimester (
Role of the Extracellular Matrix in ETC Invasion
Antibody inhibition experiments have suggested that interaction of 1ß1 integrin with Ln and collagen Type IV enhances trophoblast invasion and, conversely, that binding of
5ß1 integrin to Fn restrains invasion (
In conclusion, the differentiation of extravillous from villous trophoblast is accompanied by distinct modulation in the distribution of Ln and Fn isoforms. ETCs are characteristically associated with Ln 1, ß1, and
1, but not
2 and ß2 Ln chains. Furthermore, EDA-, EDB-, and Onc-Fns are abundantly found in the pericellular matrix of differentiating ETCs. Our results also imply that EDB- and Onc-Fns are deposited in decidual cell BMs in response to ETC invasion, and that this modification of the decidual cell basement membrane is distinct from that seen during decidualization.
![]() |
Acknowledgments |
---|
The skillful technical assistance of Ms Marja-Leena Piironen, Mr Reijo Karppinen, and Mr Hannu Kamppinen is gratefully acknowledged.
Received for publication August 7, 1996; accepted November 22, 1996.
![]() |
Literature Cited |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Aplin JD (1993) Expression of integrin 6ß4 in human trophoblast and its loss from extravillous cells. Placenta 14:203-215[Medline]
Autio-Harmainen H, Sandberg M, Pihlajaniemi T, Vuorio E (1991) Synthesis of laminin and type IV collagen by trophoblastic cells and fibroblastic stromal cells in the early human placenta. Lab Invest 64:483-491[Medline]
Badley R, Lloyd C, Woods A, Carruthers L, Allcock C, Rees D (1978) Mechanism of cellular adhesion. III. Preparation and preliminary characterization of adhesions. Exp Cell Res 117:231-244[Medline]
Benirschke K, Kaufmann P (1990) Pathology of the Human Placenta. New York, Springer-Verlag
Carnemolla B, Balza E, Siri A, Zardi L, Nicotra MR, Bigotti A, Natali PG (1989) A tumor-associated fibronectin isoform generated by alternative splicing of messenger RNA precursors. J Cell Biol 108:1139-1148[Abstract]
Castellucci M, Classen-Linke I, Mühlhauser J, Kaufmann P, Zardi L, Chiquet-Ehrismann R (1991) The human placenta: a model for tenascin expression. Histochemistry 95:449-458[Medline]
Castellucci M, Scheper M, Scheffen I, Celona A, Kaufmann P (1990) The development of the human placental villous tree. Anat Embryol 181:117-128[Medline]
Charpin C, Kopp F, Pourreau-Schneider N, Lissitzky JC, Lavaut MN, Martin PM, Toga M (1985) Laminin distribution in human decidua and immature placenta. Am J Obstet Gynecol 151:822-826[Medline]
Church HJ, Vicovac LM, Williams JDL, Hey NA, Aplin JD (1996) Laminins 2 and 4 are expressed by human decidual cells. Lab Invest 74:21-32[Medline]
Damsky CH, Fitzgerald ML, Fisher SJ (1992) Distribution patterns of extracellular matrix components and adhesion receptors are intricately modulated during first trimester cytotrophoblast differentiation along the invasive pathway, in vivo. J Clin Invest 89:210-222[Medline]
Damsky CH, Librach C, Lim K-H, Fitzgerald ML, McMaster MT, Janatpour M, Zhou Y, Logan SK, Fisher SJ (1994) Integrin switching regulates normal trophoblast invasion. Development 120:3657-3666
Earl U, Estlin C, Bulmer JN (1990) Fibronectin and laminin in the early human placenta. Placenta 11:223-231[Medline]
Engvall E, Davis GE, Dickerson K, Ruoslahti E, Varon S, Manthorpe M (1986) Mapping of domains in human laminin using monoclonal antibodies: localization of the neurite-promoting site. J Cell Biol 103:2457-2465[Abstract]
Engvall E, Earwicker D, Haaparanta T, Ruoslahti E, Sanes JR (1990) Distribution and isolation of four laminin variants; tissue restricted distribution of heterotrimers assembled from five different subunits. Cell Regul 1:731-740[Medline]
Engvall E, Wewer U (1996) Domains of laminin. J Cell Biochem 61:493-501[Medline]
Ffrench-Constant C (1995) Alternative splicing of fibronectinmany different proteins but few different functions. Exp Cell Res 221:261-271[Medline]
Frank HG, Malekzadeh F, Kertschanska S, Crescimanno C, Castellucci M, Lang I, Desoye G, Kaufmann P (1994) Immunohistochemistry of two different types of placental fibrinoid. Acta Anat 150:55-68[Medline]
Gerdes J, Schwab U, Lemke H, Stein H (1983) Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. Int J Cancer 31:13-20[Medline]
Haaparanta T, Uitto J, Ruoslahti E, Engvall E (1991) Molecular cloning of the cDNA encoding human laminin A chain. Matrix 11:151-160[Medline]
Hauptmann S, Zardi L, Siri A, Carnemolla B, Borsi L, Castellucci M, Klosterhalfen B, Hartung P, Weis J, Stöcker G, Haubeck H-D, Kirkpatrick CJ (1995) Extracellular matrix proteins in colorectal carcinomas. Expression of tenascin and fibronectin isoforms. Lab Invest 73:172-182[Medline]
Hedman K, Kurkinen M, Alitalo K, Vaheri A (1979) Isolation of the pericellular matrix of human fibroblast cultures. J Cell Biol 81:83-91[Abstract]
Hunter DD, Shah V, Merlie JP, Sanes JR (1989) A laminin-like adhesive protein concentrated in the synaptic cleft of the neuromuscular junction. Nature 338:229-234[Medline]
Iozzo RV (1995) Tumor stroma as a regulator of neoplastic behavior. Lab Invest 73:157-160[Medline]
Korhonen M, Ylänne J, Laitinen L, Cooper HM, Quaranta V, Virtanen I (1991) Distribution of the 1-
6 integrin subunits in human developing and term placenta. Lab Invest 65:347-356[Medline]
Laemmli U (1970) Cleavage of structural proteins during the assembly of the head of the bacteriophage T4. Nature 227:680-685[Medline]
Leivo I, Engvall E (1988) Merosin, a protein specific for basement membranes of Schwann cells, striated muscle, and trophoblast, is expressed late in nerve and muscle development. Proc Natl Acad Sci USA 85:1544-1548[Abstract]
Leivo I, Laurila P, Wahlström T, Engvall E (1989) Expression of merosin, a tissue-specific basement membrane protein, in the intermediate trophoblast cells of choriocarcinoma and placenta. Lab Invest 60:783-790[Medline]
Leoncini P, Betracca R, Ruggiero P, Shintorino M, Syrjänen S, Mäntyjärvi R, Syrjänen K (1990) Expression of cytokeratin No. 1 9 polypeptide in genital papillomavirus lesions Gynecol Obstet Invest 29:59-66
Liesi P, Dahl D, Vaheri A (1983) Laminin is produced by early rat astrocytes in primary culture. J Cell Biol 96:920-924[Abstract]
Marinkovich MP, Lunstrum GP, Burgeson RE (1992) The anchoring filament protein kalinin is synthesized and secreted as a high molecular weight precursor. J Biol Chem 267:17900-17906
Matsuura H, Hakomori S-I (1985) The oncofetal domain of fibronectin defined by monoclonal antibody FDC-6: its presence in fibronectins from fetal and tumor tissues and its absence in those from normal adult tissues and plasma. Proc Natl Acad Sci USA 82:6517-6521[Abstract]
Matsuura H, Takio K, Titani K, Greene T, Levery SB, Salyan MEK, Hakomori S-I (1988) The oncofetal structure of human fibronectin defined by monoclonal antibody FDC-6. J Biol Chem 263:3314-3322
Nanaev AK, Milovanov AP, Domogatsky SP (1993) Immunohistochemical localization of extracellular matrix in perivillous fibrinoid of normal human term placenta. Histochemistry 100:341-346[Medline]
Rousselle P, Lunstrum GP, Keene DR, Burgeson RE (1991) Kalinin: an epithelium-specific basement membrane adhesion molecule that is a component of anchoring filaments. J Cell Biol 114:567-576[Abstract]
Sanes JR, Engvall E, Butkowski R, Hunter DD (1990) Molecular heterogeneity of basal laminae: isoforms of laminin and collagen IV at the neuromuscular junction and elsewhere. J Cell Biol 111:1685-1699[Abstract]
Simon-Assmann P, Duclos B, Orian-Rousseau V, Arnold C, Mathelin C, Engvall E, Kedinger M (1994) Differential expression of laminin isoforms and 6-ß4 integrin subunits in the developing human and mouse intestine. Dev Dynam 201:71-85[Medline]
Timpl R, Brown JC (1994) The laminins. Matrix Biol 14:275-281[Medline]
Towbin H, Staehelin T, Gordon J (1979) Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci USA 76:4350-4354[Abstract]
Turpeenniemi-Hujanen T, Thorgeirsson UP, Rao CN, Liotta LA (1986) Laminin increases the release of type IV collagenase from malignant cells. J Biol Chem 261:1883-1889
Vartio T, Laitinen L, Närvänen O, Cutolo M, Thornell L-E, Zardi L, Virtanen I (1987) Differential expression of the ED sequence-containing form of cellular fibronectin in embryonic and adult human tissues. J Cell Sci 88:419-430[Abstract]
Virtanen I, Kallajoki M, Närvänen O, Paranko J, Thornell L-E, Miettinen M, Lehto V-P (1986) Peritubular myoid cells of human and rat testis are smooth muscle cells that contain desmin-type intermediate filaments. Anat Rec 215:10-20[Medline]
Virtanen I, Laitinen L, Vartio T (1988) Differential expression of the extra domain-containing form of cellular fibronectin in human placentas at different stages of maturation. Histochemistry 90:25-30[Medline]
Virtanen I, Lehto V-P, Lehtonen E, Vartio T, Stenman S, Kurki P, Wager O, Small JV, Dahl D, Badley RA (1981) Expression of intermediate filaments in cultured cells. J Cell Sci 50:45-63[Medline]
Virtanen I, Miettinen M, Lehto V-P, Kariniemi A-L, Paasivuo R (1985) Diagnostic application of monoclonal antibodies to intermediate filaments. Ann NY Acad Sci 455:635-648[Medline]
Vuolteenaho R, Nissinen M, Sainio K, Byers M, Eddy R, Hirvonen H, Shows TB, Sariola H, Engvall E, Tryggvason K (1994) Human laminin M chain (merosin): complete primary structure, chromosomal assignment, and expression of the M and A chain in human fetal tissues. J Cell Biol 124:381-394[Abstract]
Wewer U, Albrechtsen R, Manthorpe M, Varon S, Engvall E, Ruoslahti E (1983) Human laminin isolated in a nearly intact, biologically active form from placenta by limited proteolysis. J Biol Chem 258:12654-12660
Wewer UM, Faber M, Liotta LA, Albrechtsen R (1985) Immunochemical and ultrastructural assessment of the nature of the pericellular basement membrane of human decidual cells. Lab Invest 53:624-633[Medline]
Yamada T, Isemura M, Yamaguchi Y, Munakata H, Hayashi N, Kyogoku M (1987) Immunohistochemical localization of fibronectin in the human placentas at their different stages of maturation. Histochemistry 86:579-584[Medline]
Yamaguchi Y, Isemura M, Yosizawa Z, Kurosawa K, Yoshinaga K, Sato A, Suzuki M (1985) Changes in the distribution of fibronectin in the placenta during normal human pregnancy. Am J Obstet Gynecol 152:715-718[Medline]
Yudoh K, Matsui H, Kanamori M, Ohmori K, Tsuji H (1995) Tumor cell attachment to laminin promotes degradation of the extracellular matrix and cell migration in high-metastatic clone cells of RCT sarcoma in vitro. Jpn J Cancer Res 86:685-690[Medline]
Yeh I-T, Kurman RJ (1989) Functional and morphologic expressions of trophoblast. Lab Invest 61:1-4[Medline]