CoCSC Resist Chemotherapy Figure 1. CoCSC phenotype cells preferentially survive CPA chemotherapy. A) Phenotypic profile of UM-C4 colorectal tumors for ESA, CD44 and CD166, following exclusion of mLin2 cells. B) Formalin fixed, paraffin embedded tumor sections from CPA- or vehicle-treated control mice stained with Hematoxylin & Eosin (H&E), for proliferating Ki-67+, or for TUNEL+ dead cells. Black bar = 100 mm. C) Following randomization to normalize treatment groups at 400 mm3 at day 0, twice weekly administration of vehicle (green boxes) or 38 mg/kg CPA (red circles) commenced and tumors were measured periodically. D) Phenotypic analysis of individual tumors, displaying the percentage of human tumor cells with the ESA+CD44+ phenotype as a function of tumor size. E) Representative overlay histogram displaying CD166 surface expression on human ESA+CD44+ tumor cells from vehicle- or CPA-treated animals. The black line represents isotype control staining of ESA+CD44+ tumor cells. doi:10.1371/journal.pone.0002428.g001 and non-Hodgkins lymphoma, but is not generally used to treat colorectal cancer due to a prevailing resistance on the part of these tumors. To investigate this resistance to therapy, we explored whether CoCSC are enriched in residual tumors following CPA administration in vivo. To address this subject of interest, tumors were initiated with highly purified CoCSC from multiple xenogeneic tumor lines (UM-C4 & UM-C6) and upon reaching 3 ,400 mm , mice were randomized to receive either vehicle or PLoS ONE | www.plosone.org 3 June 2008 | Volume 3 | Issue 6 | e2428