CORRESPONDENCE

Re: Dietary Fat, Calories, and Prostate Cancer Risk

Thomas G. Pretlow

Correspondence to: Thomas G. Pretlow, M.D., Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106 (e-mail: 102426.232{at}compuserve.com).

Bosland et al. (1) describe "findings . . . based on the Dunning R3327-H rat prostate carcinoma and on LNCaP cells transplanted into SCID [severe combined immunodeficient] mice. Although these are the only androgen-sensitive prostate cancer models generally available at present, they are probably not good models for localized prostate cancer. LNCaP cells were derived from a metastatic lesion and have an uncommon androgen receptor mutation, and the Dunning R3327-H tumor was developed from a large (advanced) prostate tumor that had caused serious disease in its human host . . . ." I disagree.

As reviewed (2), there are many human, androgen-sensitive prostate cancers that grow in immunodeficient mice. In 1990, Kleinman et al. presented the first of several reports from her laboratory [reviewed in (2)] that showed that many kinds of neoplastic cells are more tumorigenic when transplanted in Matrigel into immunodeficient mice. Following the lead of Kleinman et al. (3), in 1991, we [reviewed in (2)] reported the transplantation of prostate cancers in Matrigel into nude mice. The xenografts that became serially transplantable (2,4)—CWR21, CWR22, CWR31/91, and several strains of CWR22R—have been sent to more than 100 investigators and are "generally available at present" (1). CWR21 regresses when mouse hosts are castrated, and we have not observed any subsequent relapse of CWR21. When the tumor is less than 1 g in size, CWR22 regresses completely after castration; approximately half of regressed CWR22 tumors relapse (5) 3 months to 2 years later and are designated CWR22R.

The most extravagant claim that I have encountered about the Dunning tumor is that (1) "the Dunning R3327-H tumor caused serious disease in its human host . . . ." I have detailed my views on the Dunning tumor (2). Dr. Dunning, from the University of Miami in Florida, wrote (6): "In August, 1961, a spontaneous tumor of the prostate observed at necropsy in a Copenhagen male rat . . . measured 5.0 x 4.5 x 4.0 cm . . . ." The original tumor was not examined by a pathologist. As an autopsy pathologist, I am amazed that a tumor as enormous as that described in the abdomen of a rat was dubbed prostatic in origin. Although Dunning makes nonspecific allusions (6) to cellular and ". . . electrophoretic pattern[s] . . . characteristic of dorsal gland secretion . . ." of the prostate, she does not describe the control tissues, if any, or any specific marker studied. Unlike the overwhelming majority of prostate cancers in rats, dogs, and humans (6), "blood from one rat with a tumor from the first transplanted generation showed an acid phosphatase level . . . not as high as . . . observed . . . in . . . some of the rats bearing the transplanted squamous cell carcinomas . . . ." In the absence of (a) specific markers and (b) the usual levels of acid phosphatase in the blood, a 5-cm adenocarcinoma extending from the pelvis into the abdomen of a rat is a tumor of unknown origin.

There are other reasons to question the authenticity of the Dunning tumor as a prostate cancer. As reviewed (2), in this decade, Dr. Michael Sporn and others have demonstrated that a high proportion of tumors in rodents, previously termed "prostate cancers," are cancers of the seminal vessicles, tumors that are exceedingly rare in humans. In addition, several excellent papers from G. Aumuller's laboratory (7) demonstrate that the Dunning tumor (a) has little in common with rat prostates and (b) has many properties of mammary tissue.

REFERENCES

1 Bosland MC, Oakley-Girvan I, Whittemore AS. Dietary fat, calories, and prostate cancer risk. J Natl Cancer Inst 1999;91:489-91.[Free Full Text]

2 Pretlow TG, Pretlow TP. Models of prostate cancer. In: Resnick MI, Thompson IM, editors. Advanced therapy of prostatic disease. Hamilton (ON, Canada): B. C. Decker, Inc.; 1999. p. 1-18.

3 Kleinman HK, Fridman R, Kanemoto T, Sweeney TM, Zain M, Royce L. Role of basement membrane and laminin in metastases and tumor growth [abstract]. Proc Am Assoc Cancer Res 1990;31:490-1.

4 Pretlow TG, Wolman SR, Micale MA, Pelley RJ, Kursh ED, Resnick MI, et al. Xenografts of primary human prostatic carcinoma. J Natl Cancer Inst 1993;85:394-8.[Abstract]

5 Nagabhushan M, Miller CM, Pretlow TP, Giaconia JM, Edgehouse NL, Schwartz S, et al. CWR22: the first human prostate cancer xenograft with strongly androgen-dependent and relapsed strains both in vivo and in soft agar. Cancer Res 1996;56:3042-6.[Abstract]

6 Dunning WF. Prostate cancer in the rat. Monogr Natl Cancer Inst 1963;12:351-70.

7 Goebel HW, Rausch U, Steinhoff M, Seitz J, Bacher M, Papotti M, et al. Arguments against the prostatic origin of the R-3327 Dunning H tumor. Virchows Arch B Cell Pathol Incl Mol Pathol 1992;62:9-18.[Medline]



             
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