Paracrine Factors of Human Fetal MSCs Inhibit Liver Cancer Growth Through Reduced Activation of IGF-1R/PI3K/Akt Signaling

• DOI: 10.1038/mt.2015.13
• Publication Date: 2015-01-26T12:14:42Z
• Authors: Yulyana Yulyana; Ivy A W Ho; Kian Chuan Sia; Jennifer P Newman; Xin Yi Toh; Berwini B Endaya; Jerry K Y Chan; Massimiliano Gnecchi; Hung Huynh; Alexander Y F Chung; Kiat Hon Lim; Hui Sun Leong; Narayanan Gopalak...; Kam Man Hui; Paula Y P Lam
• Keywords: Niacinamide; 0301 basic medicine; Biomedical and clinical sciences; Carcinoma, Hepatocellular; Indoles; 610; Receptor, IGF Type 1; Phosphatidylinositol 3-Kinases; 03 medical and health sciences; Fetus; Genetic; Drug Discovery; Genetics; Sunitinib; Humans; Pyrroles; Molecular Biology; Cell Proliferation; Pharmacology; Drug Discovery3003 Pharmaceutical Science; Phenylurea Compounds; Liver Neoplasms; Mesenchymal Stem Cells; Sorafenib; 3. Good health; Biological sciences; Culture Media, Conditioned; Gene Knockdown Techniques; Molecular Medicine; Proto-Oncogene Proteins c-akt; Signal Transduction

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death in world. The multikinase inhibitor sorafenib only demonstrated marginal improvement overall survival for advanced disease prompted search alternative treatment options. Human mesenchymal stem cells (MSCs) have ability to home tumor cells. However, its functional roles on microenvironment remain controversial. Herein, we showed that conditioned media derived from human fetal MSC (CM-hfMSCs) expressed high level insulin growth factor binding proteins IGFBPs and can sequester free insulin-like factors (IGFs) inhibit HCC cell proliferation. inhibitory effect IGF signaling was further evident reduction activated IGF-1R PI3K/Akt, eventually induction cycle arrest. We also CM-hfMSCs could enhance therapeutic efficacy sunitinib. To best our knowledge, this first report show has a tumor-specific, antiproliferative not observed with normal hepatocyte patient-derived matched tissues. Our results thus suggest provide useful tool design alternative/adjuvant strategies HCC, especially related function potentiate effects chemotherapeutic drugs.