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.
D000818:Animals; D001862:Bone Resorption; D002132:Calcium Radioisotopes; D002470:Cell Survival; D015232:Dinoprostone; D005354:Fibrosarcoma / Q000473:pathology* / Q000503:physiopathology / Q000648:ultrastructure; D051379:Mice; D008815:Mice, Inbred Strains; D008855:Microscopy, Electron, Scanning; D008940:Mitotic Index; D009361:Neoplasm Invasiveness; D010006:Osteoblasts / Q000503:physiopathology / Q000648:ultrastructure; D011458:Prostaglandins E / Q000494:pharmacology; D012886:Skull / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology / Q000648:ultrastructure; D012888:Skull Neoplasms / Q000473:pathology* / Q000503:physiopathology / Q000648:ultrastructure
D002132:Calcium Radioisotopes; D011458:Prostaglandins E; D015232:Dinoprostone