Analysis of Integrin α7 Mutations in Prostate Cancer, Liver Cancer, Glioblastoma Multiforme, and Leiomyosarcoma

Abstract

Integrin alpha7 appears to be a tumor suppressor that operates by suppressing tumor growth and retarding migration.

Integrins in prostate cancer progression

“…Expression of the b 1 cytoplasmic variant, b 1C , which is downregulated in prostate cancer, completely prevents tumor growth by inhibiting IGF-IR signaling (Goel et al 2004). It has also been reported that the expression of a 7 in prostate cancer cells injected subcutaneously in SCID mice suppresses tumor growth (Ren et al 2007). This observation is relevant to the human disease as analysis of a 7 in human prostate cancer reveals that a 7 is downregulated in this type of cancer and is mutated in 57% of prostate cancers; in addition, mutations in this subunit are associated with increased cancer recurrence (Ren et al 2007).…”

“…It has also been reported that the expression of a 7 in prostate cancer cells injected subcutaneously in SCID mice suppresses tumor growth (Ren et al 2007). This observation is relevant to the human disease as analysis of a 7 in human prostate cancer reveals that a 7 is downregulated in this type of cancer and is mutated in 57% of prostate cancers; in addition, mutations in this subunit are associated with increased cancer recurrence (Ren et al 2007). Pawar et al (2007) show that growth of tumors treated with fractionated doses of irradiation (3 Gy!10 days) is inhibited in PC3 cells expressing a mutated non-cleavable form of a 6 integrin.…”

“…The relative ratio of matrix metalloproteinases, cell surface proteases, such as hepsin (Klezovitch et al 2004) which is upregulated in prostate cancer, and protease inhibitors such as maspin known to be a metastasis suppressor (Li et al 2007a,b, Luo et al 2007), contribute to ECM protein cleavage. This allows tumor cells to invade connective tissues and travel out of the vasculature to distant sites (Zucker et al 2000).…”

The role of the cell adhesion molecules (integrins / cadherins) in prostate cancer

“…The expression of α6 subunit diminishes with increasing histologic grade, especially at sites of contact with the basement membrane (5). PCa demonstrates decreased positive staining for subunit α 7 , with a further decrease in metastatic disease (6). Other α subunits that have been found down-regulated include α 2 , α 4 , α 5 , and αv (2).…”

“…Studies have demonstrated expression of the heterodimeric complexes αvβ 3 and αvβ 6 , in PCa specimens in contrast with normal controls (10). Integrin α v β 3 has been demonstrated to increase cdc2 kinase activity and cdc2 levels in PCA (11).…”