CXCL7 plays a crucial role in facilitating extramedullary invasion and osteolytic damage in multiple myeloma

Abstract

The primary distinction between multiple myeloma (MM) and its precursor conditions lies in the deterioration of the biological behavior of tumor cells. In MM, a type of mature B-cell tumor, chemokines may serve as pivotal regulatory genes. Through exploration of GEO database and single-cell RNA-seq data from our laboratory, we have identified chemokines CXCL7 as a potential key regulator of the cellular biological behavior in MM. Subsets of MM cells with high CXCL7 exhibit heightened malignant potential. Elevated CXCL7 is associated with extramedullary invasion and pathological fractures in patients. In vitro, CXCL7 promoted the proliferation, invasion and migration of MM cells. Leveraging the homing ability of plasma cell, we established a mouse xenograft tumor model through vein injection of a CXCL7-overexpressing cell line. We found that MM cells with elevated CXCL7 exhibited enhanced engraftment in bone marrow, induced extramedullary lesions and increased susceptibility to leg fractures. Through exploration of intracellular signaling pathways and subsequent experiments, we observed that CXCL7 can modulate the biological behavior of MM cells by activating the IL-2-STAT5 pathway in the absence of exogenous IL-2. Our findings provide new insights into understanding the pathogenesis mechanisms underlying MM, suggesting that targeting CXCL7 may offer promising therapeutic opportunities.