Abstract
Multiple Myeloma (MM) is malignant haematological disease characterized by uncontrolled proliferation of monoclonal plasma cells (PC) in bone marrow (BM). The receptor, CXCR4 is widely expressed on hematopoietic cells including MM cells and respond to CXCL12 gradients for mobilization through blood stream and bone marrow. CXCL12 plays an important role in recruitment of MM cells to bone marrow microenvironment and formation of neoangiogenic niches supporting tumor growth, survival and metastasis. The integral role of this chemokine-receptor axis in development of MM makes it a desirable target for therapeutics. In this review, we outline the background on MM and role of specific chemokine CXCL12 in the disease with an attempt to highlight the targeted therapeutics for its signaling receptor CXCR4 in MM.
Highlights
Multiple Myeloma (MM) is malignant haematological disease characterized by uncontrolled proliferation of monoclonal plasma cells (PC) in bone marrow (BM)
We outline the background on MM and role of CXCL12/CXCR4 chemokine receptor axis in the disease with an attempt to highlight the targeted therapeutics for its signaling receptor CXCR4 in MM
AMD3100 inhibited migration in vitro and homing of MM cells in vivo, as well as downstream signaling through the phosphatidylinositol 3-kinase (PI3K)/Akt and extracellular signal-regulated kinase (ERK) signaling pathways highlighting its potential in CXCL12 and CXCR4 mediated homing of MM cells to the bone marrow [81]
Summary
Multiple Myeloma (MM) is malignant haematological disease characterized by uncontrolled proliferation of monoclonal plasma cells (PC) in bone marrow (BM). Chemokines and their receptors play roles in modulating angiogenesis [59], cell recruitment [45], tumor survival [60] and proliferation [61,62,63], and lead to progression of the cancer. The survival of these transformed cells is dependent on the bone marrow microenvironment with further demand on these cells to express distinctive chemokine receptor profiles at the site of disease activity [65,66,67,68,69].
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