Fig. 2.

Diverse fibroblast cell lines reduce lapatinib sensitivity that is mediated via secreted factors. (A) Human fibroblasts (primary lung: Wi38; primary normal breast: 1068; primary cancer-associated fibroblasts: CAF1 and CAF2; immortalized normal breast: AR22; and murine fibroblasts: 3T3) reduce lapatinib sensitivity. Representative dose–response data from at least two biological replicates for each tumor–fibroblast pair. Error bars are SD for three replicate wells. (B) Conditioned medium from normal breast fibroblasts (AR22) reduces lapatinib sensitivity. Representative experiment for three biological replicates. Error bars are SD for three replicate wells. (C) Treatment with AR22-conditioned medium confers protection from lapatinib-induced cell death. Results are representative of three biological replicates. Error bars are SD for three replicate wells. (D) Cancer cell lines that are desensitized to lapatinib in coculture (increase in normalized AUC >1) are also desensitized by conditioned medium (Pearson R² = 0.8917, P = 0.02). Error bars are SEM for three biological replicates.