Loss of VLA‐2 Collagen Receptor in Breast Carcinoma, Facilitating Invasion and Metastasis

Arihiro, Koji; Inai, Kei; Kurihara, Kanji; Takeda, Shinpei; Kaneko, Mayumi; Kuroi, Katsumasa; Toge, Tetsuya

doi:10.1111/j.1349-7006.1993.tb02036.x

Cited by 13 publications

(10 citation statements)

References 32 publications

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“…Among the ill integrin family, altered expression of ct2ill integrin has been frequently reported in malignant tumors [10,13,14,[23][24][25]. In breast cancer, expression of ~t2ill integrin is reported to be reduced compared with the normal mammary gland [26][27][28][29][30]. Its expression is correlated with differentiation [26][27][28]30] and ER expression [26,30] of breast cancer.…”

Section: Introductionmentioning

confidence: 99%

Expression and ligand binding of α2β1 integrin on breast carcinoma cells

et al. 1995

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We examined the expression and ligand specificity of the alpha 2 beta 1 integrin on human mammary epithelial cells (HMEC) and a panel of breast carcinoma cell lines in vitro. We found that the alpha 2 beta 1 integrin was universally, but quite variably expressed on these cells by FACS analysis. No significant correlation was observed between its expression and other known cellular phenotypes. Substrate attachment assays using blocking antibodies demonstrated that alpha 2 beta 1 integrin served as a receptor for collagen on HMEC and almost all breast carcinoma cells. However, its contribution to laminin binding of these cells appeared to be related to cellular differentiation as evaluated by sex steroid receptor status and by markers of epithelial-mesenchymal transition, i.e. loss of E-cadherin and expression of vimentin. Two different populations of non-malignant immortalized HMEC (184A1N4 and MCF-10A) contained cells capable of using alpha 2 beta 1 integrin as a laminin receptor. Breast cancer cell lines positive for estrogen receptor (ER) and E-cadherin (MCF-7, T47D, ZR75-1) could also use alpha 2 beta 1 integrin as a laminin receptor. Conversely, alpha 2 beta 1 integrin appeared to be incapable of binding to laminin or to be a very minor receptor for laminin on metastatic ER-negative breast carcinoma cells that expressed vimentin (MDA-MB 231, MDA-MB 435, and MDA-MB 436). These findings suggest that the ligand specificity of alpha 2 beta 1 integrin, i.e. its function as a laminin receptor, may be regulated during the malignant progression of breast carcinoma cells. A reduced contribution of alpha 2 beta 1 integrin to the cellular laminin binding appears to be associated with an increased malignant phenotype and with an epithelial-mesenchymal transition of breast carcinoma cells.

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Section: Introductionmentioning

confidence: 99%

Expression and ligand binding of α2β1 integrin on breast carcinoma cells

et al. 1995

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“…Previous published reports for a role of a 2 h 1 in metastasis, however, are controversial. a 2 h 1 expression in renal cell carcinomas was found to correlate with the malignant phenotype (34), where loss of a 2 h 1 expression in human breast cancer was associated with tumor progression (35). Overexpression of the a 2 subunit in human rhabdomyosarcoma cells led to enhanced experimental metastasis to lung (36), where enforced expression of a 2 h 1 in the same cells slowed postextravasation movement (37).…”

Section: à7mentioning

confidence: 99%

Type I Collagen Receptor (α2β1) Signaling Promotes the Growth of Human Prostate Cancer Cells within the Bone

Hall¹,

Dai²,

et al. 2006

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The most frequent site of prostate cancer metastasis is the bone. Adhesion to bone-specific factors may facilitate the selective metastasis of prostate cancer to the skeleton. Therefore, we tested whether prostate cancer bone metastasis is mediated by binding to type I collagen, the most abundant bone protein. We observed that only bone metastatic prostate cancer cells bound collagen I, whereas cells that form only visceral metastases failed to bind collagen. To confirm the relationship between collagen adhesion and bone metastatic potential, a collagen-binding variant of human LNCaP prostate cancer cells was derived through serial passage on type I collagen (LNCaP col ). Fluorescence-activated cell sorting analysis showed that LNCaP col cells express increased levels of the integrin collagen I receptor A 2 B 1 compared with LNCaP cells. Antibodies to the A 2 B 1 complex inhibited LNCaP col binding to collagen, confirming that integrins mediated the attachment. Correspondingly, LNCaP col cells displayed enhanced chemotactic migration toward collagen I compared with LNCaP cells, an activity that could be blocked with A 2 B 1 antibodies. To directly test the role of A 2 B 1 -dependent collagen binding in bone metastasis, LNCaP and LNCaP col cells were injected into the tibia of nude mice. After 9 weeks, 7 of 13 (53%) mice injected with LNCaP col developed bone tumors, whereas 0 of 8 mice injected with LNCaP cells had evidence of boney lesions. LNCaP col cells were found to express increased levels of the metastasis-promoting RhoC GTPase compared with parental LNCaP. We conclude that collagen I attachment mediated by A 2 B 1 initiates motility programs through RhoC and suggest a mechanism for prostate cancer metastasis to the bone. (Cancer Res 2006; 66(17): 8648-54)

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“…Also VLA, is probably implicated in the complex multistep suggesting that increased adhesion of tumour cells to subendothelial basement membrane components results in increased metastatic potential. In contrast, the down-regulation of VLA, is observed in poorly differentiated or larger tumours of the colon (Pignatelli et al, 1991a), liver (Patriarca et al, 1993), skin (Stamp et al, 1991) and breast Pignatelli et al, 1991b;Arihiro et al, 1993), and in prostate carcinomas (Bonkhoff et al, 1993) and melanomas (Schadendorf et al, 1993), suggesting that reduced VLA2 expression may be an indicator of predisposition to the development of metastases.…”

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confidence: 95%

“…These adhesive properties of tumour cells expressing VLA, promote the development of metastases as shown by experimental data (Chan et al, 1991) and facilitate adhesion to the vessel wall. However, the decreased expression of VLA, in human carcinomas ; Pignatelli et al, 1991a and b;Stamp and Pignatelli, 1991;Arihiro et al, 1993;Bonkhoff et al, 1993;Patriarca et al, 1993) is associated with higher metastatic rate or tumour dedifferentiation. In this respect, the VLA, expression of tumour cells in early breast carcinomas could constitute a prognostic indicator.…”

Section: Correlation Of Vla2 Expression With Quantitative Immunodetecmentioning

confidence: 99%

“…Antibody sources Anti-human VLA, (150-kDa integrin oc2 chain, anti-CD29b) mouse monoclonal (immunoglobulin G1) antibody (clone Gi9) was purchased from Immunotech (Marseille, France) and used diluted at 1:500 (Arihiro et al, 1993;Bonkhoff et al, 1993). The other monoclonal antibodies used were all commercially available and were used as described previously (Charpin et al, 1988a(Charpin et al, , 1994(Charpin et al, , 1995b(Charpin et al, , 1997a Automated immunohistochemistry Automated immunohistochemistry was used for all the monoclonal antibodies, except for anti-E cadherin (LSAB kits, Dako) (Charpin et al, 1997c) and anti-ER and anti-PR (Abbott Kits) (Charpin et al, 1988b) and was performed on consecutive sections (4 gm thick) with avidin-biotin-peroxidase complex on Ventana 320 device (Grogan et al, 1993(Grogan et al, , 1995 (Charpin et al, 1997a-d).…”

Section: Immunohistological Staining Proceduresmentioning

confidence: 99%

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VLA2 integrin expression in breast carcinomas evaluated by automated and quantitative immunohistochemistry

Charpin

García²,

Bergeret³

et al. 1998

Br J Cancer

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Summary VLA2 is thought to be involved in the metastatic process in malignant tumours, in particular in carcinomatous cell adhesion to vessel basement membrane. VLA2 expression was immunohistochemically investigated in 204 breast carcinomas. Frozen tissue sections were probed with monoclonal anti-VLA2 using automated (Ventana ES 320 System) and quantitative (SAMBA 2005 and P-glycoprotein (P-gp) (P < 0.01) and inversely correlated with cathepsin D (P < 0.001), but was independent of Ki67/MIB1, p53, bcl-2, c-erbB-2, E cadherin, CD44v, CD31, cestrogen and progesterone receptors' (ER, PR) antigenic sites and pS2. The exact role, if any, of VLA2 in tumour cell dissemination remains to be elucidated and the clinical relevance of VLA2 immunodetection in breast carcinomas requires further investigation of the correlation between VLA2 immunocytochemical expression and patients' outcome and response to chemotherapy.

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Loss of VLA‐2 Collagen Receptor in Breast Carcinoma, Facilitating Invasion and Metastasis

Cited by 13 publications

References 32 publications

Expression and ligand binding of α2β1 integrin on breast carcinoma cells

Expression and ligand binding of α2β1 integrin on breast carcinoma cells

Type I Collagen Receptor (α2β1) Signaling Promotes the Growth of Human Prostate Cancer Cells within the Bone

VLA2 integrin expression in breast carcinomas evaluated by automated and quantitative immunohistochemistry

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