Laminin alpha‐1, alpha‐3, and alpha‐5 chain expression in human prepubetal benign prostate glands and adult benign and malignant prostate glands

Brar, Preetinder; Dalkin, Bruce L.; Weyer, Chris; Sallam, Karim; Virtanen, Ismo; Nagle, Raymond B.

doi:10.1002/pros.10206

Cited by 34 publications

(33 citation statements)

References 17 publications

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“…In nonmalignant prostate ECM, LM332 is predominant [26,28,35]; the high mRNA and protein levels of the LM α3, β3, and γ2 chains observed in the PECs are consistent with previous data. LM332 has been shown to be necessary for epithelial cell polarization during development of a normal basal epithelial cell layer [36,37].…”

Section: Discussionsupporting

confidence: 92%

Senescence-Induced Alterations in the Laminin Component of Prostate Epithelial Extracellular Matrix Regulate Progression of Prostate Cancer

Sprenger¹,

Plymate²

2009

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Approved for public release; distribution unlimitedThe purpose of this work was to determine how changes in laminin chains associated with senescence affected prostate cancer progression. In order to determine the effects of alterations to the laminin component of the tumor microenvironment, I overexpressed the laminin alpha 4, beta 2, or alpha 4 and beta 2 chains in a human prostate cancer cell line. I demonstrated that these lines secreted the specific laminin chains and incorporated them into the extracellular matrix. Stable expression of the laminin alpha 4 chain resulted in increased in vitro migration and increased in vivo angiogenesis and tumorigenicity of those cells compared to empty vector control cells. High expression of both the laminin alpha 4 and beta 2 chains decreased in vitro proliferation and migration and decreased in vivo tumorigenicity compared to control cells. Stable expression of the laminin beta 2 chain alone had a tumor promoting function as opposed to the tumor suppressive role seen with high protein levels of the laminin alpha 4 and beta 2 chains together. These data support the concept that since senescent cells secrete both tumor promoting and tumor inhibiting factors, it is the interaction of these factors that infl ences cell lar beha ior This dichotom also points to the importance of nderstanding prostate cancer, senescence, microenvironment, extracellular matrix, laminins U U U UU 28 Appendices…………………………………………………………………………….…...6 USAMRMCSprenger CC -1 INTRODUCTION:Age-associated epithelial cancers, such as breast and prostate, contribute significantly to the mortality of the elderly. One mechanism by which the body defends itself against epithelial cancers is to halt replication of damaged cells by senescence, in which cells are replicatively arrested but metabolically active. We have shown that senescent prostate cancer cells specifically alter the laminin component of their extracellular matrix (ECM) (Appendix C). Laminins are ECM proteins important to both the structure and function of the microenvironment. Our cell line model of a senescent prostate cancer cell, the M12mac25 cells, displayed increased expression of the laminin α4 and β2 chains. The purpose of this study was to determine how changes in laminin chains associated with senescence affected prostate cancer progression. BODY:In order to determine the effects of alterations to the laminin component of the tumor 1. Creation of prostate cancer cell lines overexpressing various laminin chains (α4, β2 or both α4β2).2. Demonstrated secretion and deposition of these chains into the extracellular matrix; this had not been accomplished for any laminin chains in prostate cell lines before.3. The novel finding that high expression of the laminin α4 and β2 chains together in prostate cancer cells led to a 3D deposition pattern for laminins as well as other matrix proteins, such as fibronectin. Previously, 3D deposition of laminins was reported only in co-cultures of epithelial cells and fibroblasts.4. Stable expression of the ...

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Section: Discussionsupporting

confidence: 92%

Senescence-Induced Alterations in the Laminin Component of Prostate Epithelial Extracellular Matrix Regulate Progression of Prostate Cancer

Sprenger¹,

Plymate²

2009

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“…[34][35][36] In prostate, laminin types in BM were changing during prostate development and different types were observed in prepubertal, adult benign and malignant prostate glands. 37 Few other previous investigations showed decreased and disordered laminin expression in prostate carcinoma compared to benign glands. 25,29,30,[37][38][39][40] Laminin was also poorly expressed around glands with PIN, and especially accentuated loss of laminin was noted in cases with increased tenascin expression.…”

Section: Discussionmentioning

confidence: 93%

“…37 Few other previous investigations showed decreased and disordered laminin expression in prostate carcinoma compared to benign glands. 25,29,30,[37][38][39][40] Laminin was also poorly expressed around glands with PIN, and especially accentuated loss of laminin was noted in cases with increased tenascin expression. 25 Current study confirmed results of previous investigations of laminin expression in prostate carcinoma.…”

Section: Discussionmentioning

confidence: 93%

“…25 Current study confirmed results of previous investigations of laminin expression in prostate carcinoma. 25,29,30,[37][38][39][40] Laminin was decreased in carcinoma compared to adjacent peritumourous tissue and BPH while peritumourous tissue and BPH showed similar pattern of laminin expression. We found no differences in laminin expression between Gleason pattern 3 and 4 carcinomas.…”

Section: Discussionmentioning

confidence: 99%

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Myofibroblastic stromal reaction and expression of tenascin-C and laminin in prostate adenocarcinoma

Tomas

Ulamec

Hudolin

et al. 2006

Prostate Cancer Prostatic Dis

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The aim of this study was to analyse relationship between changes of the stroma and expression of tenascin-C (TN-C) and laminin in prostate carcinoma. Tenascin-C immunostaining was increased, and laminin decreased in carcinomas compared with peritumoural tissue and benign prostate hyperplasia (Po0.05). Statistical analysis confirmed connection between stromal changes and TN-C expression in prostate carcinoma (Po0.05). Gleason pattern 3 carcinomas showed more pronounced stromal reaction and TN-C expression compared with Gleason pattern 4 carcinomas (Po0.05). The main cells in prostate cancer stroma are myofibroblasts that are also responsible for tenascin production. Degradation of laminin was not connected with myofibroblastic stromal changes.

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“…Fuchs et al have shown a decrease in basement membrane staining in high Gleason grade prostatic carcinoma and complete absence of basement membrane in metastasis (4). Laminin-1 (composed of a 1 h 1 g 1 subunits) is found in normal human prostate glands (5-7) and in adult mouse prostate (8), but its expression is lost in basement membrane surrounding primary carcinoma and metastatic lymph node lesions (7). Laminin-1 is an important component of the basement membrane and is involved in epithelial cell adhesion and polarization (9).…”

Section: Introductionmentioning

confidence: 99%

β1 Integrins Modulate Cell Adhesion by Regulating Insulin-Like Growth Factor-II Levels in the Microenvironment

et al. 2006

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The interactions between cancer cells and the extracellular matrix (ECM) regulate cancer progression. The B 1C and B 1A integrins, two cytoplasmic variants of the B 1 integrin subfamily, are differentially expressed in prostate cancer. Using gene expression analysis, we show here that the B 1C variant, an inhibitor of cell proliferation, which is down-regulated in prostate cancer, up-regulates insulin-like growth factor-II (IGF-II) mRNA and protein levels. In contrast, B 1A does not affect IGF-II levels. We provide evidence that B 1C -mediated upregulation of IGF-II levels increases adhesion to Laminin-1, a basement membrane protein down-regulated in prostate cancer, and that the B 1C cytoplasmic domain contains the structural motif sufficient to increase cell adhesion to Laminin-1. This autocrine mechanism that locally supports cell adhesion to Laminin-1 via IGF-II is selectively regulated by the B 1 cytoplasmic domain via activation of the growth factor receptor binding protein 2-associated binder-1/SH2-containing protein-tyrosine phosphatase 2/phosphatidylinositol 3-kinase pathway. Thus, the concurrent local loss of B 1C integrin, of its ligand Laminin-1, and of IGF-II in the tumor microenvironment may promote prostate cancer cell invasion and metastasis by reducing cancer cell adhesive properties. It is, therefore, conceivable that reexpression of B 1C will be sufficient to revert a neoplastic phenotype to a nonproliferative and highly adherent normal phenotype. (Cancer Res 2006; 66(1): 331-42)

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Laminin alpha‐1, alpha‐3, and alpha‐5 chain expression in human prepubetal benign prostate glands and adult benign and malignant prostate glands

Abstract: Alpha 1 (Lns 1/3) is prominent in BM, but is replaced by a laminin matrix rich in alpha3 (Lns 5,6,7) and alpha5 (Lns 10/11) in benign adult prostate glands. In carcinoma, both alpha1 (Lns-1/3) and alpha3 (Lns 5,6,7) are not expressed with persistence of a BM rich in alpha5 (Lns 10/11).

Cited by 34 publications

References 17 publications

Senescence-Induced Alterations in the Laminin Component of Prostate Epithelial Extracellular Matrix Regulate Progression of Prostate Cancer

Senescence-Induced Alterations in the Laminin Component of Prostate Epithelial Extracellular Matrix Regulate Progression of Prostate Cancer

Myofibroblastic stromal reaction and expression of tenascin-C and laminin in prostate adenocarcinoma

β1 Integrins Modulate Cell Adhesion by Regulating Insulin-Like Growth Factor-II Levels in the Microenvironment

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