Enhanced caveolin-1 expression increases migration, anchorage-independent growth and invasion of endometrial adenocarcinoma cells

Abstract

BackgroundCaveolin-1 (CAV1) has been implicated both in tumor suppression and progression, whereby the specific role appears to be context dependent. Endometrial cancer is one of the most common malignancies of the female genital tract; however, little is known about the role of CAV1 in this disease.MethodsHere, we first determined by immunohistochemistry CAV1 protein levels in normal proliferative human endometrium and endometrial tumor samples. Then using two endometrial cancer cell lines (ECC: Ishikawa and Hec-1A) we evaluated mRNA and protein levels of CAV1 by real time qPCR and Western blot analysis, respectively. The role of CAV1 expression in ECC malignancy was further studied by either inducing its expression in endometrial cancer cells with the tumor promotor 12-O-tetradecanoyl-phorbol-13-acetate (4β-TPA) or decreasing expression using short-hairpin RNA constructs, and then evaluating the effects of these changes on ECC proliferation, transmigration, matrigel invasion, and colony formation in soft agar.ResultsImmunohistochemical analysis of endometrial epithelia revealed that substantially higher levels of CAV1 were present in endometrial tumors than the normal proliferative epithelium. Also, in Ishikawa and Hec-1A endometrial cancer cells CAV1 expression was readily detectable. Upon treatment with 4β-TPA CAV1 levels increased and coincided with augmented cell transmigration, matrigel invasion, as well as colony formation in soft agar. Reduction of CAV1 expression using short-hairpin RNA constructs ablated these effects in both cell types whether treated or not with 4β-TPA. Alternatively, CAV1 expression appeared not to modulate significantly proliferation of these cells.ConclusionOur study shows that elevated CAV1, observed in patients with endometrial cancer, is linked to enhanced malignancy of endometrial cancer cells, as evidenced by increased migration, invasion and anchorage-independent growth.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1477-5) contains supplementary material, which is available to authorized users.

Caveolin‐1, cancer and therapy resistance

“…33,35,36 Nevertheless, for several tumors CAV1 upregulation influences cancer cell survival and growth, favoring tumor progression (summarized in Table 1). [37][38][39] As an assumption, the prognostic value of CAV1 depends on cell specificity, cell transformation, tumor stage, the physiological context and most importantly on the nature of the tumor stroma. A loss of CAV1 in several tumor cells seems to induce a hyper-proliferative state, promoting cell proliferation, angiogenesis and tumor progression ( Fig.…”

Comparison of the Immunohistochemical Expression of Caveolin-1 in Endometrial Carcinoma, Endometrial Intraepithelial Neoplasia, Endometrial Hyperplasia, and Normal Endometrium

“…As documented in various studies, Cav-1 protein detected in different neoplasms has a complex and controversial role in cell proliferation, tumor development, and progression. 14,15 It has been also shown that Cav-1 expression decreases during development of breast, ovary, colon, and lung tumors. 14 Besides, re-expression of Cav-1 alters the transformed phenotype of mammary, colon and ovarian carcinoma cells.…”

“…14,15 It has been also shown that Cav-1 expression decreases during development of breast, ovary, colon, and lung tumors. 14 Besides, re-expression of Cav-1 alters the transformed phenotype of mammary, colon and ovarian carcinoma cells. [15][16][17] As a tumor suppressor protein Cav-1 promotes cell death possibly by blocking signaling pathways aberrantly activated in cancer cells.…”

Expression of Caveolin-1 in Human Cutaneous and Uveal Melanoma Cells

“…CAV-1 expression was evaluated by Real-time RT-PCR (Applied Biosystems StepOnePlus Real-time PCR system). The following primers were used (300 nM each): CAV-1 forward 5'-TGGTTTTACCGCTTGCTGTCTG-3', CAV-1 reverse 5'-GCAAGTTGATGCGGACATTGCT-3' (DIAZ-VALDIVIA et al 2015). The general conditions of experiment were the same as described by BUBKA et al (2014).…”