Periostin potently promotes metastatic growth of colon cancer by augmenting cell survival via the Akt/PKB pathway

Abstract

Molecular mechanisms associated with tumor metastasis remain poorly understood. Here we report that acquired expression of periostin by colon cancer cells greatly promoted metastatic development of colon tumors. Periostin is overexpressed in more than 80% of human colon cancers examined with highest expression in metastatic tumors. Periostin expression dramatically enhanced metastatic growth of colon cancer by both preventing stress-induced apoptosis in the cancer cells and augmenting endothelial cell survival to promote angiogenesis. At the molecular level, periostin activated the Akt/PKB signaling pathway through the alpha(v)beta(3) integrins to increase cellular survival. These data demonstrated that the survival-promoting function is crucial for periostin to promote tumor metastasis of colon cancer.

Periostin promotes invasiveness and resistance of pancreatic cancer cells to hypoxia-induced cell death: role of the β4 integrin and the PI3k pathway

“…By in situ hybridisation, we identified the tumour cells as the unique source of production of periostin while immunohistochemical analysis demonstrates the presence of periostin only in the juxtatumoral stroma. This is the first report where stromal localization of periostin is described as previous studies have reported localization of periostin in the cytoplasm of other types of cancer cells (Gillan et al, 2002;Bao et al, 2004;Shao et al, 2004;Kim et al, 2005;Tai et al, 2005). Although, we have occasionally detected a cytoplasmic immunoreactivity of periostin in PDAC cells, the stromal localization was always dominant.…”

“…These results are corroborated by the observation that the interaction between astrocytoma cells and big-h3, a protein homologue of periostin, is dependent on a 6 b 4 integrin (Kim et al, 2003). Previous studies reported that the a v b 3 and a v b 5 integrin complexes act as the receptors for periostin in breast, colon and ovarian cancer as well as endothelial cells (Gillan et al, 2002;Bao et al, 2004;Shao et al, 2004). These two integrin complexes are however not expressed in the majority of pancreatic tumour cell lines in vitro (data not show) and only 50% of PDAC tissue specimens express detectable levels of a v b 3 in vivo (Hall et al, 1991;Hosotani et al, 2002).…”

“…Recent reports have shown that periostin interacts with the a v b 3 integrin in tumour cells (Gillan et al, 2002;Bao et al, 2004) and as a v b 3 integrin is known to regulate the expression of proteases, we next sought to determine the effect of overexpression of the a v b 3 in CFPac1 cells on the induction of proteases induced by periostin. The a v -positive CFPac1 cells were infected with a b 3 integrin-expressing retrovirus (Morgan et al, 2004) and elevated expression of the a v b 3 integrin complex confirmed by flow cytometry (Figure 4d, left panel).…”

Periostin differentially induces proliferation, contraction and apoptosis of primary Dupuytren's disease and adjacent palmar fascia cells

“…Myofibroblasts have been shown to utilize the PI3 kinase/Akt signaling pathway to avoid apoptosis in abnormal scarring [66][67][68] and periostin signaling has been shown to promote avoidance of apoptosis through this pathway [29,37]. While there was a consistent trend towards a decrease in DD cells apoptosis with periostin treatment, this did not achieve statistical significance in our in vitro collagen culture conditions (DD cells treated with vehicle vs. 0.5 μg/ml recombinant periostin, p=0.075; PF cells treated with vehicle vs. 2.0 μg/ml recombinant periostin, p=0.065).…”

“…Periostin is highly expressed during the earliest stages of bone fracture repair [15] and vascular injury [16] and periostin signaling induces the expression of molecules associated with cutaneous wound repair such as collagen and fibronectin [17,18]. A role in cancer cell metastasis has also been suggested, as periostin is a recognize component of stromal reactions in a variety of tumor types [19][20][21][22][23][24][25][26][27][28][29]. While DD shares some characteristics with each of these repair and disease processes, the role(s) of periostin in this fibromatosis is yet to be determined.…”