Figure 2.
Breast cancer cells are poor producers of autotaxin (ATX) compared to adjacent adipose tissue tumor-associated fibroblasts. (A) Human breast cancer cells express little ATX compared to other neuroblastoma, melanoma, glioma, thyroid, and liver cancer cells. Results are means ± SEM. Numbers in parentheses indicates the number of cell lines. Results taken from cBioPortal (www.cbiportal.org) [63,64] and are reproduced from Reference [29] with permission. (B) ATX mRNA expression in 176 human breast tumors and 10 normal breast tissue specimens. Box plots show minimum, mean, and maximum values, 25th, 50th, and 75th percentiles (box), and 1st and 99th percentiles. Results are expressed relative to the mean of the breast tumor results, which were given the value of 1. * p < 0.001. Adapted from Reference [67]. (C) ATX, mRNA, and activity levels are significantly lower in tumors compared to adjacent fat pads in orthotopic syngeneic and immunocompetent mouse models (4T1/BALB/C, E0771/C57BL/6) * p < 0.05 by a paired t-test. Results are expressed relative to the mean of the breast tumor results, which were given the value of 1. Includes results adapted from Reference [14]. (D) Relative ATX mRNA and activity levels in patient-matched Hs578T breast cancer cells and Hs578Bst stromal cells. Results are means ± SEM from three independent experiments. * p < 0.05 vs. Hs578T breast cancer cells. Adapted from Reference [67]. (E) ATX expression in mouse 4T1 tumors comes predominantly from cancer-associated fibroblasts. Whole 4T1 tumors were enzymatically digested and sorted by flow cytometry for cancer cells (epithelial cells) using EPCAM (epithelial cell adhesion molecule), leukocytes using CD-45, endothelial cells using CD-31, and cancer-associated fibroblasts using platelet-derived growth factor alpha (PDGFα). ATX mRNA levels are expressed relative to those in the whole tumor. Results are means ± SEM from three independent experiments for whole tumor and cancer cells, and means ± range for two independent experiments for leukocytes, endothelial cells, and fibroblasts.