title: The role of alpha 6 beta 1 integrin and EGF in normal and malignant acinar morphogenesis of human prostatic epithelial cells.
abstract: Complex multiple interactions between cells and extracellular matrix occur during acinar morphogenesis involving integrin receptors and growth factors. Changes in these interactions occur during carcinogenesis as cells progress from a normal to a malignant, invasive phenotype. We have developed human prostatic epithelial cell lines of the same lineage, which represent multiple steps in carcinogenesis, similar to prostatic intraepithelial neoplasia and subsequent tumor progression. The non-tumorigenic, RWPE-1 and the tumorigenic WPE1-NB27 and WPE1-NB26 cell lines were used to examine their ability to undergo acinar morphogenesis in a 3-D cell culture model and its relationship to invasion, integrin expression and EGF presence. An inverse relationship between the degree of acinar formation and invasive ability was observed. The non-tumorigenic, non-invasive RWPE-1 and the low tumorigenic, low invasive, WPE1-NB27 cells show high and decreased acinar forming ability, respectively, while the more invasive WPE1-NB26 cells show a loss of acinar formation. While RWPE-1 acini show basal expression of alpha 6 beta 1 integrin, which correlates with their ability to polarize and form acini, WPE1-NB27 cells lack alpha 6 but show basal, but weaker expression of beta 1 integrin. WPE1-NB26 cells show loss alpha 6 and abnormal, diffused beta 1 integrin expression. A dose-dependent decrease in acinar formation was observed in RWPE-1 cells when cell proliferation was induced by EGF. Anti-functional antibody to EGF caused an increase in acinar formation in RWPE-1 cells. These results suggest that malignant cells lose the ability to undergo acinar morphogenesis and that the degree of this loss appears to be related to invasive ability, EGF levels and alterations in laminin-specific integrin expression. This model system mimics different steps in prostate carcinogenesis and has applications in the secondary and tertiary prevention of prostate cancer.
authors.affiliation: Department of Zoology, S-350 Plant Biology Building, Michigan State University, East Lansing, MI 48824-1312, USA.
authors.forename: D
authors.initials: D
authors.lastname: Bello-DeOcampo
authors.forename: H K
authors.initials: HK
authors.lastname: Kleinman
authors.forename: M M
authors.initials: MM
authors.lastname: Webber
mesh_terms: D000906:Antibodies / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D003094:Collagen; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D039121:Integrin alpha6beta1; D016023:Integrins / Q000378:metabolism*; D007797:Laminin; D008297:Male; D009024:Morphogenesis / Q000187:drug effects; D009361:Neoplasm Invasiveness / Q000473:pathology; D011230:Precancerous Conditions / Q000378:metabolism* / Q000473:pathology; D011467:Prostate / Q000166:cytology / Q000378:metabolism*; D019048:Prostatic Intraepithelial Neoplasia / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D011509:Proteoglycans
chemical_list: D000906:Antibodies; D004338:Drug Combinations; D039121:Integrin alpha6beta1; D016023:Integrins; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D004815:Epidermal Growth Factor; D003094:Collagen