Lymph Node Stromal Cells Enhance Drug-Resistant Colon Cancer Cell Tumor Formation through SDF-1α/CXCR4 Paracrine Signaling

• DOI: 10.1593/neo.11324
• Publication Date: 2015-04-23T13:04:47Z
• Authors: David A. Margolin; Jennifer Silinsky; Chelsea Grimes; Nakia Spencer; Melissa Aycock; Heather Green; Jose Cordova; Nancy K. Davis; Tiffany Driscoll; Li Li
• Keywords: Male; 0301 basic medicine; 610; Mice, SCID; Mice; 03 medical and health sciences; Antigens, CD; Cell Movement; Mice, Inbred NOD; Cell Line, Tumor; Paracrine Communication; Animals; Humans; AC133 Antigen; RC254-282; Cell Proliferation; Glycoproteins; Neovascularization, Pathologic; Neoplasms. Tumors. Oncology. Including cancer and carcinogens; Chemokine CXCL12; 3. Good health; Oncology; Drug Resistance, Neoplasm; Colonic Neoplasms; Lymph Nodes; Peptides; Neoplasm Transplantation

Colorectal cancer (CRC) is the third most common malignancy and second leading cause of cancer-related deaths in America. Nearly two thirds newly diagnosed CRC cases include lymph node (LN) involvement, LN metastasis one strongest negative prognostic factors for CRC. It thought that tumors contain a small population drug-resistant tumor-initiating cells (Co-TICs) may be responsible recurrence. To evaluate effects stromal on Co-TICs, we established unique xenoplant model using isolated by enzymatic digestion from consented patient specimens, HT-29 cells, HCA-7 cell line HK cells. We found cell-conditioned media enhanced tumor formation angiogenesis. Cells expressing CD133+ cell-derived factor 1α (SDF-1α) receptor CXCR4 were enriched chemotherapeutic-resistant CD133+CXCR4+ Co-TICs specimens are more tumorigenic than unsorted Furthermore, inhibitors specific to SDF-1α reduced Our results have demonstrated role growth defined influence Co-TICs. identified major Co-TIC/LN microenvironment-specific mechanism resistance chemotherapeutic agents experimental platforms both vitro vivo testing, indicating its receptor, CXCR4, targets clinical therapy.