Abstract 1443: BMP-2 induces motility and invasiveness of colon cancer through upregulation of cancer stem cell

Abstract

Abstract The majority of deaths in cancer patients are will present with metastasis and relapses. One of the key steps in metastasis is the migration, and Cancer stem cells(CSCs) activate migration. So, targeting of CSC is an important strategy for cancers. Bone morphogenetic protein(BMP) signaling, member of the TGF-β superfamily, plays an important role in development of bone and in regulation of stem cell properties. In Previous study, Bone morphogenetic protein(BMP) signaling has been associated with various types of cancers. BMPs contributes through autocrine and paracrine mechanisms to tumor development, invasion and metastasis. However, their roles and mechanisms are unclear. In this study, we investigated the function of BMP-2 and relevance BMP-2 and CSCs in Colon cancer cells. First, We compared the endogenous protein level of parental and spheroid cells by western blotting. The spheroid cells showed higher level of EMT(Epithelial mesenchymal transition) markers N-Cadherin and Snail, CSC markers (EpCAM and CD133), and p Smad1/5 known BMP-2 downstream than the corresponding parental cells. Then expression of EpCAM and CD133 was confirmed by flow cytometry. We found that BMP-2 plays a key role in Cancer stem cell. To determine function of BMP-2 in Colon cancer cells, we stimulated the colon cancer cells with recombinant human BMP-2. Stimulation of BMP-2 increased EMT, CSC markers(EpCAM and CD133). In addition, BMP-2 enhanced cell motility, and invasiveness by wound healing and matrigel invasion assay. These results indicated BMP-2 signaling pathway enhance metastasis through increase of CSC portion. Blockade of BMP-2 pathway by Noggin(BMP2 antagonist) or Smad1/5 siRNA inhibited BMP2-induced EMT marker, MMP2, and CSC portion. The morphologic changes though the EMT process were monitored by immunofluorescence staining and Western blot for EMT markers. And Blockade of BMP-2 pathway inhibited cell motility and invasiveness. Our findings suggest that BMP-2 signaling regulates metastatic potential through regulation of CSCs in colon cancer cell. Citation Format: Bo Ram Kim, Jung Lim Kim, Seong Hye Park, Yoon A Jeoung, Sun Il Lee, Byoung-Wook Min, Sang Cheul Oh. BMP-2 induces motility and invasiveness of colon cancer through upregulation of cancer stem cell. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1443. doi:10.1158/1538-7445.AM2015-1443