Beta 1 integrin subunit
(ITGB1)

CD29
Fibronectin receptor, beta polypeptide (FNRB)
Fibronectin receptor, beta subunit (FNRB)
Very late T-cell antigen beta (VLA-beta)

Gene: FNRB maps to 10p11.2.
mRNA: size: ~4.2 kb.
Protein: the ITGB1 cDNA encodes a 798-amino acids (aa) polypeptide, including a 20-aa signal sequence , a 23-aa hydrophobic sequence (transmembrane domain) near the carboxy terminus, 58 cysteine residues, and 12 potential N-glycosylation (Asn-X-Ser/Thr) sites (Argraves W.S. et al., 1987).

Cell lines:
- The alpha₂beta₁ integrin was expressed de novo in a poorly differentiated mammary carcinoma that expressed no detectable alpha₂-integrin subunit. Expression of the alpha₂beta₁ integrin resulted in a dramatic phenotypic alteration from a fibroblastoid, spindle-shaped, non-contact-inhibited, motile, and invasive cell to an epithelioid, polygonal-shaped, contact-inhibited, less motile, and less invasive cell. Although expression of the alpha₂ subunit did not alter adhesion to collagen, it profoundly altered cell spreading. Re-expression of the alpha₂beta₁ integrin restored the ability to differentiate into gland-like structures in three-dimensional matrices and markedly reduced the in vivo tumorigenicity of the cells (Zutter M.M. et al., 1995).

- In breast cancer cell (BCC) lines, a reduced contribution of alpha₂beta₁ integrin to the cellular laminin binding appeared to be associated with an increased malignant phenotype and with an epithelial-mesenchymal transition (Maemura M. et al., 1995).

- MDA-MB-231 BCC were observed to adhere to quiescent human umbilical vein endothelial cells (HUVEC) monolayers in vitro, particularly at endothelial cell-cell junctions. Adhesion was reduced by pretreatment of either tumour cells or HUVEC with antibodies against beta₁ integrins. Simultaneous treatment of HUVECs and tumour cells with these antibodies produced an additive blocking effect, consistent with a heterotypic adhesion mechanism (Price E.A. et al., 1996).

- An involvement of alpha₃beta₁ integrin in the local degradation and phagocytosis of the extracellular matrix by BCC was shown (Coopman P.J. et al., 1996).

- It was found that expression of the alpha₃beta₁ integrin on metastatic BCC was specifically increased in comparison to non-metastatic cells, and that alpha₃beta₁ was involved in the increased adhesion of metastatic cells to lymph node fibronectin (FN) and in cell spreading on FN-coated substrates (Tawil N.J. et al., 1996).

- When compared to MCF-7, T-47D, ZR-75-1 BCC lines, highly tumorigenic MDA-MB-231 BCC expressed relatively high levels of ITGB1. The attachment of MDA-MB-231 cells to plastic coated with serum-free conditioned medium of human bone cells was significantly prevented by an anti-ITGB1 function-blocking antibody. This antibody also inhibited attachment of MDA-MB-231 BCC to trabecular bone at later developmental stages, but not to hypertrophic cartilage (van der Pluijm G. et al., 1997).

- Melatonin, the principal pineal gland hormone, exerts a direct antiproliferative effect on estrogen-responsive MCF-7 BCC in culture. Melatonin could shift MCF-7 cells to a lower invasive status by increasing the beta1 integrin subunit and E-cadherin expression and promoting the differentiation of tumor cells (Cos S. et al., 1998).

- Study with a panel of MDA-MB-231 and other BCC lines showed a close correlation between alpha₂beta₁ and alpha₃beta₁ integrin receptor expression and the capability to attach to cortical bone (Lundström A. et al., 1998).

- The phenotypic characteristics of 2 BCC lines (BC-H1 and BC-K1) established from bone marrow of patients with breast cancer were studied by immunocytochemistry, flow cytometry, and RT-PCR. Both cell lines expressed E-cadherin, vimentin, cytokeratins (including component 18), alpha 5-, alpha V-, beta 1-, and beta 3- integrin subunits, ICAM-1, MCAM, LFA-3 (CD58), and CD44s (but not CD44v5, v6, v7/8). BC-H1 also expressed ErbB2 (not found in BC-K1), and MAGE-4 (but not MAGE-1, -2, -3/6, -12; BC-K1 was not tested). The expressed molecules might be potential candidates for novel therapeutic targets (Putz E. et al., 1999).

- An urokinase (uPA)-induced increase in MCF-7 BCC migration was observed selectively on vitronectin-coated surfaces and was mediated by a beta₁-integrin (probably alpha_Vbeta₁) and alpha_Vbeta₅ (Nguyen D.H. et al., 1999).

- Tetraspanins (or proteins from the transmembrane 4 superfamily, TM4SF) form membrane complexes with integrin receptors and are implicated in integrin-mediated cell migration. Alpha₃beta₁-tetraspanin protein complexes were shown to control invasive migration of MDA-MB-231 BCC by using at least two phosphoinositide 3-kinase (PI3K)-dependent signaling mechanisms: through rearrangement of the actin cytoskeleton and by modulating the MMP2 production (Sugiura T. and Berditchevski F., 1999).

Tumors:
- Cryostat sections from 12 benign and 61 malignant (50 ductal and 11 lobular) breast cancer samples were analyzed with monoclonal antibodies to the beta₁, beta₃, beta₄, and beta₅ subfamilies. All integrin subunits studied were significantly reduced on breast cancer compared with benign cells (chi-squared test) but were not related to tumor differentiation. Loss of alpha₁beta₁, alpha₂beta₁, alpha₃beta₁, alpha₆beta₁, alpha_Vbeta₁, and alpha_Vbeta₅ were related to the presence of axillary metastasis. Independently the integrins were of limited clinical value as predictors of axillary spread. However, on multivariate analysis the combination of beta₁, alpha_V, alpha₁, tumor size, and vascular invasion gave a cumulative overall accuracy in predicting nodal disease of 97% (Gui G.P. et al., 1995).

Argraves W.S. et al. (1987) Amino acid sequence of human fibronectin receptor. J. Cell Biol. 105, 1183-1190.
Coopman P.J. et al. (1996) Integrin alpha 3 beta 1 participates in the phagocytosis of extracellular matrix molecules by human breast cancer cells. Mol. Biol. Cell. 7, 1789-1804.
Cos S. et al. (1998) Influence of melatonin on invasive and metastatic properties of MCF-7 human breast cancer cells. Cancer Res. 58, 4383-4390.
Goodfellow P.J. et al. (1989) Assignment of the gene encoding the beta-subunit of the human fibronectin receptor (beta-FNR) to chromosome 10p11.2. Ann. Hum. Genet. 53, 15-22.
Gui G.P. et al. (1995) Integrin expression in primary breast cancer and its relation to axillary nodal status. Surgery 117, 102-108.
Liapis H. et al. (1996) Integrin alpha_Vbeta₃ expression by bone-residing breast cancer metastases. Diagn. Mol. Pathol. 5, 127-135.
Lundström A. et al. (1998) The role of alpha2 beta1 and alpha3 beta1 integrin receptors in the initial anchoring of MDA-MB-231 human breast cancer cells to cortical bone matrix. Biochem. Biophys. Res. Commun. 250, 735-740.
Maemura M. et al. (1995) Expression and ligand binding of alpha 2 beta 1 integrin on breast carcinoma cells. Clin. Exp. Metastasis 13, 223-235.
Nguyen D.H. et al. (1999) Myosin light chain kinase functions downstream of Ras/ERK to promote migration of urokinase-type plasminogen activator-stimulated cells in an integrin-selective manner. J. Cell Biol. 146, 149-164.
Price E.A. et al. (1996) beta-1 Integrins mediate tumour cell adhesion to quiescent endothelial cells in vitro. Br. J. Cancer 74, 1762-1766.
Putz E. et al. (1999) Phenotypic characteristics of cell lines derived from disseminated cancer cells in bone marrow of patients with solid epithelial tumors: establishment of working models for human micrometastases. Cancer Res. 59, 241-248.
Pytela R. et al. (1986) Platelet membrane glycoprotein IIb/IIIa: member of family of arg-gly-asp-specific adhesion receptors. Science 231, 1159-1162.
Sugiura T. and Berditchevski F. (1999) Function of alpha3beta1-tetraspanin protein complexes in tumor cell invasion. Evidence for the role of the complexes in production of matrix metalloproteinase 2 (MMP-2). J. Cell Biol. 146, 1375-1389.
Tawil N.J. et al. (1996) Integrin alpha3beta1 can promote adhesion and spreading of metastatic breast carcinoma cells on the lymph node stroma. Int. J. Cancer 66, 703-710.
van der Pluijm G. et al (1997) Attachment characteristics and involvement of integrins in adhesion of breast cancer cell lines to extracellular bone matrix components. Lab. Invest. 77, 665-675.
Zutter M.M. et al. (1995) Re-expression of the alpha 2 beta 1 integrin abrogates the malignant phenotype of breast carcinoma cells. Proc. Natl. Acad. Sci. USA 92, 7411-7415.

About integrins, beta 3, beta 5, alpha V