Beta 3 integrin subunit
(ITGB3)

CD61
Platelet glycoprotein IIIa (GP3A)

Gene: GP3A (ITGB3) maps on chromosome 17q21.1-q21.3. It has 14 exons ranging in size from 87 to 430 nucleotides, which are separated by introns ranging in size from 0.3 to 9 kb. The 3-prime exon is larger than 1,700 nucleotides and contains the 3-prime untranslated region (Lanza F. et al., 1990).
mRNA: sizes: 4.1 and 5.9 kb.
Protein: the cDNA encodes a 788-amino acids (aa) polypeptide including a 26-aa signal peptide, a 29-aa transmembrane domain near the carboxy terminus, and 4 tandemly repeated cysteine-rich domains of 33-38 aa (Zimrin A.B. et al., 1988).

Cell lines:
- Purified bone sialoprotein (BSP), recombinant human BSP fragments and BSP-derived RGD peptides were shown to elicit migratory, adhesive, and proliferative responses in the MDA-MB-231 BCC line. Experiments with integrin-blocking antibodies demonstrated that BSP-RGD-induced migration utilizes the alpha_Vbeta₃ vitronectin receptor, whereas adhesion and proliferation responses were alpha_Vbeta₅-mediated (Sung V. et al., 1998).

- the phenotypic characteristics of 2 tumor cell 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).

- Alpha_Vbeta₃ was found to be highly expressed on MCF-7 BCC transfected with protein kinase C-alpha (MCF-7-PKC-alpha BCC), but was undetectable on MCF-7V BCC (MCF-7 BCC transfected with vector only). In contrast, MCF-7-PKC-alpha BCC had reduced expression of alpha_Vbeta₅. Blocking experiments with antibodies to alpha_Vbeta₃ and alpha_Vbeta₅ revealed that these receptors were used by MCF-7-PKC-alpha BCC to adhere primarily to vitronectin and osteopontin. Consistent with heterodimer expression, MCF-7-PKC-alpha cells expressed increased beta₃ and decreased beta₅ on their surface. Surface expression of alpha_V on MCF-7-PKC-alpha BCC was unchanged. Western blotting, Northern analysis, and nuclear run-on assays indicated that post-translational mechanisms increased the surface expression of beta₃ on MCF-7-PKC-alpha BCC. In contrast, reduced beta₅ transcription diminished beta₅ surface expression on MCF-7-PKC-alpha BCC (Carey I. et al., 1999).

Tumors:
- Immunohistochemistry and in situ hybridization were performed in a systematic study of 22 bone biopsies containing breast cancer metastases and available samples of corresponding primary tumors and normal breast. An overexpression of alpha_Vbeta₃ was found in bone-residing breast cancer cells, suggesting either subclonal selection of alpha_Vbeta₃-expressing tumor cell populations or upregulation of alpha_Vbeta₃ in the bone microenvironment (Liapis H. et al., 1996).

- In a series of 197 consecutive patients with invasive breast cancer and long follow-up, vascular expression of integrin alpha_Vbeta₃ in tumor vascular ''hot spots'' was found to be the most significant prognostic factor predictive of relapse-free survival in both node-negative and node-positive patients (Gasparini G. et al., 1998).

Carey I. et al. (1999) Overexpression of protein kinase C-alpha in MCF-7 breast cancer cells results in differential regulation and expression of alphavbeta3 and alphavbeta5. Int. J. Oncol. 15, 127-136.
Gasparini G. et al. (1998) Vascular integrin alpha(v)beta3: a new prognostic indicator in breast cancer. Clin. Cancer Res. 4, 2625-2634.
Lanza F. et al. (1990) Characterization of the human platelet glycoprotein IIIa gene: comparison with the fibronectin receptor beta-subunit gene. J. Biol. Chem. 265, 18098-18103.
Liapis H. et al. (1996) Integrin alpha_Vbeta₃ expression by bone-residing breast cancer metastases. Diagn. Mol. Pathol. 5, 127-135.
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.
Sung V. et al. (1998) Bone sialoprotein supports breast cancer cell adhesion proliferation and migration through differential usage of the alpha(v)beta3 and alpha(v)beta5 integrins. J. Cell Physiol. 176, 482-494.
Van Cong N. et al. (1989) Assignment of GP3A gene to chromosome 17 (somatic cell hybrid analysis), region q21.1-q21.3 (in situ hybridization). (Abstract) Cytogenet. Cell Genet. 51, 1096-1097.
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.
Zimrin A.B. et al. (1988) Structure of platelet glycoprotein IIIa: a common subunit for two different membrane receptors. J. Clin. Invest. 81, 1470-1475.

About integrins, beta 1, beta 5, alpha V