Abstract 3917: PDGF induces cell growth and glycolysis in colon cancer

Abstract

Abstract The platelet derived growth factor (PDGF) plays an important role in several solid tumors. Involved in cell migration and proliferation primarily of stromal cells in cancers PDGF represents a key target in cancer therapy. The aim of this study was to analyze the specific role of PDGF on tumor cell proliferation and metabolism in colorectal cancer (CRC). The human colon cancer cell line HT-29 was cultured and stimulated time-dependently with PDGF. Additionally, inhibition of the PI3k/Akt/mTOR-pathway was performed simultaneously to PDGF stimulation. Whole cell and RNA extracts were analyzed by Western Blot and RT-q-PCR for the PI3k/Akt/mTOR-pathway and components of cellular metabolism. To investigate the effects of PDGF on proliferation MTS assays were performed. Additionally, mRNA levels of PDGF and metabolic factors in tumors from patients with CRC were analyzed by RT-qPCR. PDGF stimulation resulted in increased HT29 cell proliferation compared to untreated controls. Blocking of Akt resulted in inhibition of pS6, activation of Retinoblastoma (Rb) and reduced tumor cell growth. Additionally, under stimulation a higher glycolytic rate was observed while oxygen consumption remained unaltered. Investigated tumors from patients with CRC showed a stage-dependent increase in PDGF expression and a boosted glycolytic rate. The cytokine PDGF induced proliferation accompanied with an altered glycolysis in HT-29 colon cancer. An increased glycolysis and tumor cell proliferation support accelerated cell proliferation and tumor growth. The growth reducing effect of Akt inhibition indicates the PI3K/Akt/mTOR-pathway to play a crucial role in CRC progression and therefore could be an important target in cancer therapy. Note: This abstract was not presented at the meeting. Citation Format: Romana Moench, Vinicius Kannen, Tanja Grimmig, Christoph T. Germer, Martin Gasser, Ana Maria Waaga-Gasser. PDGF induces cell growth and glycolysis in colon cancer. [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 3917. doi:10.1158/1538-7445.AM2015-3917