Depletion of stromal cells expressing fibroblast activation protein-α from skeletal muscle and bone marrow results in cachexia and anemia

• DOI: 10.1084/jem.20122344
• Publication Date: 2013-05-28T01:00:41Z
• Authors: Edward W. Roberts; Andrew Deonarine; James O. Jones; Alice E. Denton; Christine Feig; Scott K. Lyons; Marion Espeli; Matthew Kraman; Brendan McKenna; Richard J.B. Wells; Qi Zhao; Otavia L. Caballero; Rachel Larder; Anthony P. Coll; Stephen O’Rahilly; Kevin M. Brindle; Sarah A. Teichmann; David A. Tuveson; Douglas T. Fearon
• Keywords: Lymphopoiesis; Bone marrow failure; Immunosurveillance

Fibroblast activation protein-α (FAP) identifies stromal cells of mesenchymal origin in human cancers and chronic inflammatory lesions. In mouse models cancer, they have been shown to be immune suppressive, but studies their occurrence function normal tissues limited. With a transgenic line permitting the bioluminescent imaging FAP+ cells, we find that reside most adult mouse. from three sites, skeletal muscle, adipose tissue, pancreas, highly similar transcriptomes, suggesting shared lineage. muscle are major local source follistatin, bone marrow express Cxcl12 KitL. Experimental ablation these causes loss mass reduction B-lymphopoiesis erythropoiesis, revealing essential functions maintaining hematopoiesis, respectively. Remarkably, altered at sites transplantable spontaneous cancer-induced cachexia anemia. Thus, cell may roles two adverse consequences cancer: acquisition by tumors cause failure immunosurveillance, alteration contributes paraneoplastic syndromes