RELATIONSHIP BETWEEN BONE RESORBING ACTIVITY & COLONY

实体瘤通常与骨质增加有关。 再吸收和高钙血症。 骨质增加的机制 吸收是肿瘤细胞产生的体液因子，或 刺激骨细胞骨吸收的因子。 最近， 我们和其他人已经注意到， 因为高钙血症通常与白细胞增多有关， 同时产生集落刺激活性。 为了确定导致高钙血症的因素， 这些肿瘤，我们的方法将是使用体外生物测定， 骨吸收的基础上释放先前纳入 器官培养中的45 Ca，以表征骨吸收因子 存在于肿瘤细胞培养基中，并确定 这些因素与肿瘤产物之间的关系 负责刺激集落形成的白细胞增多， 小鼠骨髓单个核细胞在甲基 纤维素. 我们计划评估骨骼和 再吸收活性和集落刺激活性， 来自肿瘤细胞的培养基，所述肿瘤细胞来源于患有 上颌骨鳞状细胞癌，仅表现为 白细胞增多症，从鳞状细胞癌患者的 仅表现为高钙血症的上颌骨， 患有舌鳞状细胞癌， 高钙血症和白细胞增多症。 这些肿瘤是由 初步结果显示，只有那些 与集落刺激活性产生有关的原因 白细胞增多症，仅与骨吸收相关的白细胞增多症 活动产生引起高钙血症。 由于细胞来源于 从这些肿瘤中分离出来，我们计划 进一步纯化骨吸收活性和殖民地， 刺激这些肿瘤产生的活性，并确定 殖民地刺激活性与已知菌落的关系 刺激因子（CSF）。 我们希望这些研究能够 阐明肿瘤细胞增加骨生成的机制 骨吸收和引起白细胞增多，并可能导致 确定影响骨密度和骨密度正常因素 骨吸收和白细胞分化。

Solid tumors are frequently associated with increased bone resorption and hypercalcenia. The mechanism for increased bone resorption is production by the tumor cells of a humoral factor or factors which stimulate osteoclastic bone resorption. Recently, we and others have noted that tumors of the oral cavity which cause hypercalcenia are often associated with leukocytosis, concomitantly with the production of colony stimulating activity. In order to identify the factors responsible for hypercalcemia in these tumors, our approach will be to use an in vitro bioassay for bone resorption based on the release of previously incorporated 45Ca in organ culture to characterize the bone resorbing factors present in the tumor cell culture media, and determine the relationship between these factors and the tumor products responsible for leukocytosis which stimulate colony formation in cultures of mouse bone marrow mononuclear cells in methyl cellulose. We plan to evaluate the relationships between bone resorbing activity and colony stimulating activity by examining culture media from tumor cells derived from a patient with squamous cell carcinoma of the maxilla who manifested only leukocytosis, from a patient with squamous cell carcinoma of the maxilla who manifested only hypercalcemia, and from a patient with squamous cell carcinoma of the tongue who manifested both hypercalcemia and leukocytosis. These tumors have been carried in nude mice and preliminary results show that only those associated with colony stimulating activity production cause leukocytosis, and only those associated with bone resorbing activity production cause hypercalcemia. Since cells derived from these tumors are now maintained in culture, we plan to purify further the bone resorbing activity and the colony stimulating activity produced by these tumors, and determine the relationship of the colony stimulating activity to known colony stimulating factors (CSFs). Our hope is that these studies will clarify the mechanisms by which tumor cells increase osteoclastic bone resorption and cause leukocytosis, and may lead to identification of normal factors which influence both osteoclastic bone resorption and leukocyte differentiation.