Home LiteratureArticle Details
PMID: 8548870 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S. Review

The alpha 6 beta 1 and alpha 6 beta 4 integrins in human prostate cancer progression.

Cancer metastasis reviews ·Vol. 14 ·No. 3 ·1995-09-00 ·Pages 219-28

Cress AE, Rabinovitz I, Zhu W, Nagle RB

Abstract

Prostatic secretions are formed by glands composed of basal and luminal cells and surrounded by a basal lamina. The normal basal cells express several integrins (extracellular matrix receptors) including alpha 2, 3, 4, 5, 6, v, beta 1 and beta 4. These integrin units are polarized at the base of the cells adjacent to the basal lamina. The integrin alpha 6 beta 4 is associated with hemidesmosomal-like structures. The natural history of prostate cancer involves the presence of prostatic intraepithelial neoplasia (PIN) lesions (considered precursor lesions), carcinoma in situ and invasive carcinoma. Hemidesmosomal proteins and the alpha 3 beta 1 and alpha 6 beta 1 integrins (laminin receptors) are retained in the early PIN lesions. Expression of the integrins alpha 2, alpha 4, alpha 5, alpha v and beta 4 is lost in carcinoma. The alpha 3 beta 1 and alpha 6 beta 1 integrins remain associated with invasive carcinoma, the latter being predominant. Integrin expression in carcinoma is diffuse in the plasma membrane and not restricted to the basal aspects of the cell. The alpha 6 beta 1 integrin is fully functional as judged by an ability to adhere to laminin and contains the wild type alpha 6A cytoplasmic signaling domain. The alpha 6 beta 1 integrin is a leading candidate for conferring the invasive phenotype in prostatic carcinoma. Tumor cells with high expression of alpha 6 integrin are more invasive when tested in a SCID mouse model system. Following intraperitoneal injection, the human tumor cells invade the mouse diaphragm and move through the muscle on the surface of the laminin coated muscle cells. Our current working hypothesis is that the production of alpha 6 beta 1 and laminin in human tumor cells contributes to the invasive phenotype. Invasion could occur on the surfaces of laminin coated structures such as the nerves, blood vessels or muscle and account for the known patterns of human prostate tumor progression. Blockage of the expression or function of alpha 6 beta 1 or laminin or preventing the loss of beta 4 would be essential steps in confining the carcinoma to the prostate gland where conventional treatment has already proven effective.

MeSH Terms
Amino Acid Sequence Animals Antigens, Surface/metabolism Disease Progression Humans Integrin alpha6beta1 Integrin alpha6beta4 Integrins/metabolism Male Mice Molecular Sequence Data Neoplasm Invasiveness Prostatic Neoplasms/metabolism,pathology
Chemicals
Antigens, Surface Integrin alpha6beta1 Integrin alpha6beta4 Integrins
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Cress A E
Department of Radiation Oncology and Pathology, University of Arizona Cancer Center, Tucson 85724, USA.
Rabinovitz I
Zhu W
Nagle R B
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Article Info
Journal
Cancer metastasis reviews
Abbr.
Cancer Metastasis Rev
ISSN
0167-7659
DOI
10.1007/BF00690293
Published
1995-09-00
Pages
219-28
Language
English
Region
Netherlands
NLM ID
8605731
Subset
IM
Grants
NCI NIH HHS · CA 23074 · United States
NCI NIH HHS · CA 56666 · United States
External Links
PubMed source DOI: 10.1007/BF00690293 View journal details
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