Hypercalcemic VX-2 carcinoma in rabbits: a clinicopathologic study.
Rabbits receiving intramuscular injections of VX-2 carcinoma cells in biceps femoris muscles developed rapidly progressive neoplastic growths at 14 to 21 days associated with a significant hypercalcemia. The biologic behavior of the VX-2 carcinoma was characterized by local infiltration and metastases to regional lymph nodes and lungs. No metastases to skeletal tissues were evident. Femora from intramuscularly injected rabbits had varying degrees of osteophytosis and lysis evident roentgenographically. Histopathologic evaluation of femoral sections revealed periosteal new bone growth, cortical osteolysis, endosteal new bone growth, and in a few long term rabbits, pathologic fractures. Bone lesions were evident histologically in the vicinity of neoplastic growth (i.e., femora, tibiae) but not at distant sites (i.e., humeri and vertebrae). Mineral analyses of VX-2 carcinoma tissues and kidneys from VX-2-bearing rabbits revealed concentrations of calcium 83 and 3 times greater, respectively, than those of skeletal muscle and kidneys from controls. These findings correlated well with histochemical evidence of excessive amounts of calcium in sections of kidneys and VX-2 carcinoma tissues. Rabbits receiving intraperitoneal injections of VX-2 carcinoma cells did not develop hypercalcemia despite an extensive, progressive neoplastic burden with metastases to abdominal and thoracic viscera. Roentgenographic, histopathologic, and physiochemical analyses of selected bones from these rabbits revealed no significant alterations. These findings indicate that VX-2 carcinoma cells need to be in close proximity to skeletal tissues in order to induce hypercalcemia. The development of a significant hypercalcemia in intramuscularly injected rabbits precedes the invasion of osseous tissues by VX-2 carcinoma cells. Therefore, it appears that VX-2 carcinoma cells have the ability to alter skeletal morphology and physiochemistry through a dual humoral/cellular mechanism. The clinicopathologic characteristics of the VX-2 carcinoma in the rabbit suggest that the neoplasm is a good experimental model to study osseous-mediated hypercalcemia of malignancy.