| First Author | Muppala S | Year | 2021 |
| Journal | Int J Cancer | Volume | 148 |
| Issue | 8 | Pages | 2010-2022 |
| PubMed ID | 33320955 | Mgi Jnum | J:303831 |
| Mgi Id | MGI:6508456 | Doi | 10.1002/ijc.33439 |
| Citation | Muppala S, et al. (2021) Thrombospondin-4 mediates hyperglycemia- and TGF-beta-induced inflammation in breast cancer. Int J Cancer 148(8):2010-2022 |
| abstractText | Inflammation drives the growth of tumors and is an important predictor of cancer aggressiveness. CD68, a marker of tumor-associated macrophages (TAM), is routinely used to aid in prognosis and treatment choices for breast cancer patients. We report that thrombospondin-4 (TSP-4) mediates breast cancer inflammation and growth in mouse models in response to hyperglycemia and TGF-beta by increasing TAM infiltration and production of inflammatory signals in tumors. Analysis of breast cancers and noncancerous tissue specimens from hyperglycemic patients revealed that levels of TSP-4 and of macrophage marker CD68 are upregulated in diabetic tissues. TSP-4 was colocalized with macrophages in cancer tissues. Bone-marrow-derived macrophages (BMDM) responded to high glucose and TGF-beta by upregulating TSP-4 production and expression, as well as the expression of inflammatory markers. We report a novel function for TSP-4 in breast cancer: regulation of TAM infiltration and inflammation. The results of our study provide new insights into regulation of cancer growth by hyperglycemia and TGF-beta and suggest TSP-4 as a potential therapeutic target. |
