Multicellular tumor spheroid interactions with bone cells and bone

In vitro coculture techniques were used to study HSDM1C1 murine fibrosarcoma multicellular tumor spheroid (HSDM1C1‐MTS) interactions with mouse calvarial bone cells having osteoblastic characteristics and mouse bone explants. HSDM1C1‐MTS attached to confluent bone cell monolayers and their attachment rate was quantified. HSDM1C1‐MTS interaction with bone cells was further demonstrated by the release of 3H‐deoxyuridine from prelabeled bone cells during coculture with multicellular tumor spheroids. HSDM1C1‐MTS‐induced cytotoxicity was mimicked by the addition of 10−5 M prostaglandin E2 (PGE2) to 3H‐deoxyuridine‐labeled bone cells. The effects of low (10−9 M) and high (10−5 M) concentrations of PGE2 on bone cell proliferation were also studied. Higher concentrations of PGE2 inhibited bone cell proliferation. HSDM1C1‐MTS resorbed living explants in the presence of indomethacin, suggesting that other tumor cell products may also participate in bone resorption. HSDM1C1‐MTS caused direct bone resorption as measured by the significantly elevated release of 45Ca from prelabeled, devitalized calvaria. However, the growth of a confluent bone cell layer on devitalized, 45Ca‐prelabeled calvaria resulted in a significant reduction in the amount of 45Ca released subsequent to the seeding of HSDM1C1‐MTS onto the explants. Bone cells at the bone surface may act as a barrier against invasion and tumor cell‐mediated bone resorption. Violation of this cellular barrier is achieved, in part, by tumor cell products.