SPP1 and plasma cell myeloma: Cell-cell contact between myeloma tumor cells and osteoclasts causes release of factors such as IL-6 and osteopontin that support myeloma growth.(9,20) Osteoclasts also release angiogenic factors (including osteopontin) that work in concert with other bone marrow factors to enhance angiogenesis.(34) This link between bone turnover and angiogenesis may be one reason that myeloma presents as such a highly angiogenic disease and may also explain the high rate of relapse and chemoresistance characteristic of myeloma.