Abstract 3405: Caveolin-1 modulates the metastatic ability of Ewing's sarcoma

Abstract

Abstract Metastasis is the final stage of tumor progression and is thought to be responsible for up to 90% of deaths associated with solid tumors. Caveolin-1 (CAV1) regulates multiple cancer-associated processes including cellular transformation, tumor growth, cell death and survival, multidrug resistance, angiogenesis, cell migration and metastasis. Although CAV1 was previously identified as a metastasis-associated gene that is a transcriptional target of EWS/FLI1 as well as an important determinant of Ewing's sarcoma family of tumors (ESFT) malignant phenotype, the possible involvement of CAV1 in regulating the ability of ESFT to metastasize has not been established. Therefore, in the present study we tested the hypothesis that CAV1 modulates the metastatic ability of ESFT cells. First, we analyzed the expression of CAV1 by immunostaining a tissue microarray (TMA) containing 43 paraffin-embedded ESFT tumors with known EWS translocations. Even though no evidence was found for a significant association between CAV1 expression with stage, size or tumor site, all metastatic samples (10/10) had significantly high CAV1 expression, suggesting that high CAV1 content makes it easier for ESFT cells to metastasize. To determine the effect of CAV1 on the migratory and invasive capabilities of ESFT cells, we knocked down CAV1 expression in TC252 and A673 cells by stably transfecting a previously validated shRNA construct. In vitro, wound healing and transwell migration and invasion assays showed that, in both cell lines. CAV1 knocked-down cells migrated significantly less (p≤0.01) than parental and vector-transfected control cells. Moreover, control transfected A673 cells introduced into balb/c nude mice by tail vein injection strongly colonized the lungs. In contrast, about 40% of animals injected with low CAV1 cells had no incidence of metastasis to any organ, and the other 60% suffered a significant delay in lung colonization (P=0.0005). These data demonstrate that CAV1 plays a key role in regulating the ability of ESFT cells to metastasize. Ongoing experiments are designed to elucidate the CAV1-regulated signalling pathways responsible for the development of ESFT metastases. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3405.