Arguments against the prostatic origin of the R-3327 Dunning H tumor (original) (raw)
Related papers
Basal cells of H-Dunning tumor are myoepithelial cells
Histochemistry, 1991
Recent immunohistochemical studies have shown that basal cells in human prostatic epithelium are not myoepithelial cells. Since in the literature the Dunning tumor, originally described as a rat prostate carcinoma derived from the dorsolateral prostate of a Copenhagen rat, was reported to have myoepithelial cells, a comparative immunohistochemical and ultrastructural study was performed in the H-, HIF-and ATa-lines of the Dunning tumor, the male accessory sex glands (ventral, dorsal, lateral prostate, coagulating gland, bulbourethral gland) and the mammary gland of both Copenhagen and Wistar rats. Mono-and polyclonal antibodies directed against intermediate filament proteins (cytokeratin, desmin, vimentin) and the contractile proteins (c~-actin, muscle type specific myosin, tropomyosin) were used along with phalloidin decoration of F-actin. As in the human prostate, none of the rat prostate lobes in either strain did contain basal cells expressing cytokeratin along with c~-actin, myosin and tropomyosin. Cells representing fully differentiated myoepithelial cells, however, were present as anticipated in the mammary gland, the bulbourethral gland and the Htumor line of the Dunning tumor. This finding is difficult to reconcile with the contention of a prostatic origin of the H-Dunning tumor. Further studies are required to classify the epithelial parental tissue in order to define the true origin of the H-Dunning tumor and the tumor lines derived thereof.
Cancer research, 1987
The Dunning R3327 tumor represents a system for studying prostate cancer in Copenhagen X Fischer rats. Animals bearing variant sublines (H, G, and MAT-LyLu) differing in growth rate, differentiation, hormone responsiveness, and metastatic ability were assayed for three immunological markers. Spleens were passed through a tissue sieve, and mononuclear cells were obtained by Ficoll-Hypaque centrifugation. These were assayed for leukocytic subsets using monoclonal antibodies. An adherent population was isolated and evaluated using thin-layer chromatography for conversion of radiolabeled arachidonic acid to E series prostaglandins. Finally, sera from these animals were assayed for levels of circulating immune complexes using polyethylene glycol precipitation. Data from 52 rats bearing the various tumors were obtained, correlated with subline aggressiveness, and compared to 15 controls. Each tumor group demonstrated significantly lower helper/suppressor T-cell ratios than controls, proba...
International Urology and Nephrology, 1998
Prostatic epithelium basically consists of secretory-luminal, basal and endocrine-paracrine cells. Immunohistochemical procedures are frequently used for showing the cells reflecting different differentiations. In this study, 40 prostatic tissue specimens submitted to the Department of Pathology of In0niJ University, Research Hospital, between 1991 and 1996 were examined. Half of the cases were diagnosed as cancer and the other half had various benign lesions. Of the cases 22.5% (n = 9) were needle biopsy material whereas the remainder, 47.5% (n = 19), were from prostatectomy and 30% (n = 12) were transurethral resection of the prostate (TURP) specimens. High molecular weight anti-cytokeratin antibodies (HMW anti-cytokeratin) stained basal cells both in all normal prostatic tissue and benign prostatic lesions, but in the majority of cancers (70%, n = 14) negative immunoreactivity was seen. Nevertheless, in some of the cancer cases (30%, n = 6) basal cell anti-cytokeratin staining was shown. Negative immunoreactivity with HMW anti-cytokeratin is important in distinguishing between malignant and benign lesions, whereas positive staining is not every time in favour of benign lesions. With the usage of prostate specific antigen (PSA) it was seen that all of the malignant and benign prostatic lesions stained positively. Basal cells in hyperplastic glands were not stained with this stain. Irregular, and in some areas, intense (PSA) immunoreactivity is present in precancerous and malignant lesions. Endocrine cells, which are represented with Chromogranin-A (Chr-A) immunoreactivity and reflecting neuroendocrine differentiation, are present in 75% (n = 15) of benign lesions and in 50% (n = 10) of cancer cases. It was thought that the lesser number of these cells in neoplastic lesions in comparison to the non-tumoral lesions is correlated with the disorder of mechanism that regulates the cell growth. Both in neoplastic and nontumoral tissues the prostatic epithelial cells showed the three markers, namely HMW anti-cytokeratin, PSA, and Chr-A, which may reflect the multidirectional differentiation of these cells from a pluripotent origin.
Gross and microscopic pathology of induced prostatic complex tumors arising in Lobund-Wistar rats
Cancer research, 1994
The necessity for additional animal models for prostate cancer has recently been stressed. The Pollard model of chemically induced prostate cancer has received attention in this regard although the histiogenetic origin of these tumors has come under question. We independently studied this model for the development of tumors in the prostate region. The tumors, all of which were adenocarcinomas, first became grossly evident 5 months after induction and ultimately occurred in 71% of the animals. Seventy-three % of the tumors involved only the seminal vesicle, 22% involved other portions of the prostatic complex as well as the seminal vesicle, and 5% were located in the coagulating gland (anterior prostate). Although the majority of tumors arose in or involved the seminal vesicle, this may still be a useful model for the study of human prostate cancer because the tumors are adenocarcinomas, occur in the large majority of animals, are hormonally induced, and have the propensity to metast...
Neuroendocrine differentiation in human prostatic tumor models
American Journal Of Pathology
benign and malignant prostatic epithelia. Factors regulating their presence and their functions arepoorly understood, mainly due to a lack of suitable experimental models. Fifteen in vitro and in vivo prostatic cancer tumor models, including a number of newly established in vivo models, were studied immunohistochemicaly for the presence ofNE cells under different hormonal conditions. None of the in vitro models (PC-3, DU 145, LNCaP, and TSU) contained NE cells. Five of the seven xenograft models established at this laboratory contained NE cells. In three of these, NE cells were found only in the initial mouse passages. In the other two (PC-295 and PC-310), the NE phenotype was stable. NE features were confirmed by transmission electron microscopy and by Western analysis of chromogranin A expression. Immunohistochemical double-labeling experiments confirmed that NE cells in prostate cancer are post-mitotic (no Ki-67 expression) and do not express the androgen receptor. In the PC-295 and PC-310 models, short-term androgen withdrawal resulted in a rapidly increased number of NE cells. A time course experiment with PC-295-bearing mice strongly suggests that this increase occurred by induction of NE differentiation rather than by rapid proliferation and subsequent differentiation or selective persistence. In conclusion, these models are suitable to resolvefundamental questions with regard to the presence andfunctions of NE cells in human prostate cancer. (Am J Pathol 1996, 149:859 -8 71) Neuroendocrine (NE) or endocrine-paracrine cells are characterized by a number of structural, cytochemical, and functional properties.1 The dispersed NE system consists of single or clustered NE cells located in the epithelium of several non-NE organs (lungs and gastrointestinal tract).2 The normal prostate likewise contains epithelial NE cells belonging to this system. Prostatic NE cells secrete neuropeptides and biogenic amines (reviewed by Noordzij et al3). In concordance with the functions of NE cells in other epithelial organs, it has been suggested, but not proven, that prostatic NE cells play a role in the maintenance of homeostasis and/or regulation of secretion of prostatic glandular epithelium.4 In addition, there is some evidence that these cells have exocrine functions as well.56 NE cells are present in the majority of prostate cancers.7 It is of importance to distinguish three types of NE differentiation within prostate cancer. Small-cell prostate cancer and prostatic carcinoid are relatively rare and are considered pure NE tumors with a poor prognosis.8 Conventional adenocarcinoma with scattered or clustered NE cells represents the most common type of prostate cancer with NE differentiation. The NE cells in both benign and malignant prostatic epithelium can be identified immunohistochemically with antibodies against products secreted by these cells or by routine transmission electron microscopy that visualizes the neurosecretory granules (also known as dense core granules or NE granules).9 Chromogranin A (CgA) is a 68-kd acidic glycoprotein that is secreted by most, if not all, NE cells. It may play a role in the excretory pathway of neuropeptides and is most likely a precursor of several functional peptides (eg, pancreastatin and chromostatin) that are formed by proteolytic cleavage of the CgA molecule.12,13 Anti-
The isolation and characterization of epithelial cells from canine prostate
1998
A protein receptor tyrosine kinase (RTK 6) has been isolated from a complementary DNA library of SKOV-3, an epithelial ovarian cancer cell line, using a polymerase chain reaction (PCR)-mediated approach. The primary structure of the predicted amino acid sequence of the protein shows a novel NH2-terminal region which has homology to a factor VIII-like domain. The juxtamembrane region is proline and glycine rich and is the longest for any known receptor kinase. The COOHterminal catalytic domain has all of the canonical sequence motifs of a receptor tyrosine kinase with homology to the TRK-2H protein (49%). A single transcript of 4.5 kilobases is expressed at low levels in heart, placenta, lung, liver, muscle, kidney, and pancreas, with high levels of expression in the brain. Ribonuclease protection assay showed a varying level of expression of message in a panel of eight ovarian cancer cell lines compared to placenta. In situ hybridization analysis demonstrated localization of mRNA in the epithelial cells of the ovary, kidney, small bowel, lung, thymus, and brain. There was a lower level of message in normal, benign, and borderline tumors of the ovary compared to malignant tumors of the ovary. Polyclonal antisera raised against a COOH-terminal synthetic peptide recognize a Mr 140,000 protein in ovarian cancer cells, which autophosphorylates in an in vitro kinase assay.
Human Pathology, 2000
confirmed sulfated glycosaminoglycans of similar structure as the main constituent of both PSG and corpora amylacea. Peripheral zone amphiphilic "dark cell" carcinoma (9 cases) contained almost no PSG, and showed neither apical decapitation nor EB formation, but mucin secretion was frequently detected. Crystalloids that share the same staining characteristics and sulfur content as PSG and corpora amylacea were identified in 3 selected "clear cell" carcinomas, all of which showed at least focal PSG secretion. The recognition of these differing secretory mechanisms and their deviation from normal further defines the histological criteria and spectrum of prostate malignancy. HUM PATROL 31:94-100.
Veterinary and Comparative Oncology, 2021
A limited number of species, including men and dogs, spontaneously develop prostate cancer (PC). The histological and molecular relevance of canine PC as a model for the disease in men remains controversial. To address this challenge, this study aimed to assess the histomorphology and expression of basal cell, urothelial and neuroendocrine markers [p63, high molecular weight cytokeratin (HMWCK), Uroplakin 3 (UPIII), neuron-specific enolase (NSE)] in canine PC (n = 41). Based on histomorphology, 10/41 (24%), 21/41 (51%) and 9/41 (22%) were classified as adenocarcinoma (AC), urothelial carcinoma (UC), and mixed carcinoma, respectively. Tumour inflammation was common, frequently severe [20/41 (49%)], and associated with neutering (p < .02) and urothelial differentiation (p < .02). Most (36/40, 90%) cancers contained only rare cells with basal cell marker expression or were negative. The expression of UPIII was absent or weak in the majority (33/38, 87%) of tumours, with moderate to strong staining in the remaining cases. NSE expression in PC was rare and limited to 2/14 (14%) cases. Tumour extension into benign ducts and glands was a common finding with presence in 17/39 (44%) of carcinomas with and without urothelial differentiation. In conclusion, we confirm that canine PC is characterized by absent or weak expression of basal cell and urothelial markers. Although rare, NSE expression, potentially indicating neuroendocrine differentiation, is reported for the first time in canine PCa. Intraductal carcinoma of the prostate with concurrent invasive PCa (IDCP-inv) is a frequent, not previously described, finding in dogs with PC.