Abstract 3337: Characterization of tumor initiating cells response to chemotherapy in human colorectal cancer

• Published in: Cancer research (Chicago, Ill.) Vol. 70; no. 8_Supplement; p. 3337
• Main Authors: da Silva-Diz, Victoria, Riba-Artés, Diana, Gausachs, Mireia, Urpí, María, Capella, Gabriel, Salazar, Ramón, Villanueva, Alberto, Muñoz, Purificación
• Format: Journal Article
• Language: English
• Published: 15.04.2010
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM10-3337

Abstract Current chemotherapy for colorectal cancer is still based in combined 5-fluorouracil (5-FU) and oxaliplatin administration with or without other new drugs. However, an important percentage of patients show resistance to this treatment. Tumor initiating cells (TICs) or cancer stem cells, are able to reconstitute a tumor of similar characteristics to the primary tumor after transplantation into immunodeficient mice. TICs show the ability to self-renew and give rise to non-TIC progeny, supporting the tumor growth. Recent studies suggest that TICs may be intrinsically resistant to therapy, leading to tumor relapse after chemotherapy. To gain insight into the dynamics of TICs during tumor progression and in response to chemotherapy, we have orthotopically implanted and perpetuated in nude mice 14 human colorectal carcinomas (CRC) that produce local and distal dissemination. We have characterized the chemotherapy response in 7 of these perpetuated xenografts. Four of these tumors showed a significant reduction of growth after 5-FU and oxaliplatin combined treatment (FUOX treatment) compared to the correspondent non-treated control tumors. To evaluate the role of TICs in chemotherapy response, we analyzed survival of non-TICs and TICs -identified by CD133/CD44/EpCAM cell surface markers- after chemotherapy. Our results show that, although in 2 out of 4 of the tumors showing efficient response to chemotherapy, TICs were more resistant to FUOX than the rest of tumor cells, in the other 2 tumors TICs and non-TICs were similarly sensitive to treatment. These results indicate that the resistance to chemotherapy is not an intrinsic characteristic of TICs and offer the possibility to characterize sensitive and resistant TICs to FUOX to identify genes and pathways directly involved in chemoresistance. 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 3337.