Roberts, E. W., Deonarine, A., Jones, J. O., Denton, A. E., Feig, C., Lyons, S. K., Espeli, M., Kraman, M., McKenna, B., Wells, R. J. B., Zhao, Q., Caballero, O. L., Larder, R., Coll, A. P., O'Rahilly, S., Brindle, K. M., Teichmann, S. A., Tuveson, D. A., Fearon, D. T. (June 2013) Depletion of stromal cells expressing fibroblast activation protein-alpha from skeletal muscle and bone marrow results in cachexia and anemia. Journal of Experimental Medicine, 210 (6). pp. 1137-1151. ISSN 0022-1007
Abstract
Fibroblast activation protein-alpha (FAP) identifies stromal cells of mesenchymal origin in human cancers and chronic inflammatory lesions. In mouse models of cancer, they have been shown to be immune suppressive, but studies of their occurrence and function in normal tissues have been limited. With a transgenic mouse line permitting the bioluminescent imaging of FAP(+) cells, we find that they reside in most tissues of the adult mouse. FAP(+) cells from three sites, skeletal muscle, adipose tissue, and pancreas, have highly similar transcriptomes, suggesting a shared lineage. FAP(+) cells of skeletal muscle are the major local source of follistatin, and in bone marrow they express Cxcl12 and KitL. Experimental ablation of these cells causes loss of muscle mass and a reduction of B-lymphopoiesis and erythropoiesis, revealing their essential functions in maintaining normal muscle mass and hematopoiesis, respectively. Remarkably, these cells are altered at these sites in transplantable and spontaneous mouse models of cancer-induced cachexia and anemia. Thus, the FAP(+) stromal cell may have roles in two adverse consequences of cancer: their acquisition by tumors may cause failure of immunosurveillance, and their alteration in normal tissues contributes to the paraneoplastic syndromes of cachexia and anemia.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | experimental cancer cachexia phase-ii trial food-intake myostatin mice atrophy differentiation adenocarcinoma glycoprotein specificity |
| Subjects: | diseases & disorders > cancer diseases & disorders diseases & disorders > bone diseses |
| CSHL Authors: | |
| Communities: | CSHL Cancer Center Program > Signal Transduction CSHL labs > Fearon lab CSHL labs > Tuveson lab CSHL labs > Lyons lab |
| Depositing User: | Matt Covey |
| Date: | June 2013 |
| Date Deposited: | 19 Jul 2013 15:52 |
| Last Modified: | 11 May 2017 20:43 |
| PMCID: | PMC3674708 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/28448 |
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