LETTER |
Correspondence to: Pedro Esbrit, Unidad de Investigación, Fundación Jiménez Díaz, Avda. Reyes Católicos 2, 28040 Madrid, Spain.
Parathyroid HORMONE-RELATED PROTEIN (PTHrP) was initially isolated from tumors associated with humoral hypercalcemia of malignancy and has since been identified in many normal tissues, in which it appears to act as an auto/paracrine growth/differentiation factor (
Neurons from different subregions of the rat brain, including the cerebellum and the hippocampus, express PTHrP and PTH/PTHrP receptors (
Four low-grade astrocytomas and five high-grade astrocytomas (
Immunostainings were performed with anti-PTHrP antisera C6 and C13, recognizing the C- and N-terminal region of PTHrP, respectively (
Positive immunostaining for PTHrP was found in all nine astrocytomas with antisera C6 and C13. With either antiserum, the staining was diffuse in the cytoplasm of neoplastic cells and was prominent in the larger cells with a more astrocytic appearance (Figure 1A and Figure 1B). These cells were abundant in the five high-grade astrocytomas, whose proliferative activity, expressed as percentage of MIB 1-positive nuclear area was (mean ± SD) 17 ± 5%, greater than 5 ± 3% in the four low-grade cases. Adjacent non-neoplastic cortex in the tissue samples did not stain for PTHrP. No immunostaining was observed on incubation without these primary antisera (Figure 1C).
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One of the tumors, an astrocytoma of high grade 4, was selected to further characterize PTHrP by Western immunoblotting. A fresh tumor sample (1.2 g) was extracted with 0.2 M HCl/8 M urea/0.1 M cysteine and then with 0.1 M NaCl/20% ethanol/10 mM acetic acid (
All our cases of astrocytoma were normocalcemic at presentation. In this regard, several studies indicate that PTHrP expression can occur in a variety of tumors in the absence of hypercalcemia (
PTHrP is widely expressed during normal fetal development and is present in various adult tissues, in which it appears to modulate cell growth and/or differentiation (
In the rat, the PTH/PTHrP receptor, but not PTHrP, is highly expressed in cortical astrocytes, in which PTHrP[134] induces a process-bearing cell morphology and increases cellular glial fibrillary acidic protein (
Taken together, the latter findings and our present results suggest that production of PTHrP by human astrocytomas may be associated with dysregulated mechanisms of growth and/or differentiation in malignant astrocytoma cells. Elucidation of the factors that induce PTHrP expression and its role in these tumor cells await further studies.
Acknowledgments
Supported in part by a grant from Fondo de Investigación Sanitaria of Spain (FIS 94/269). F. de M. is the recipient of a fellowship from the Spanish Ministry of Health (BAE 95/5438).
We thank Ms Trinidad Carrizosa for her technical assistance.
Received for publication April 10, 1997; accepted October 22, 1997.
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