Author Nakanishi M, Ide M, Kawashima M, Kuwamura M, Kumagai D, Sawamoto O, Yamate J.
Title Establishment of a transplantable rat pulmonary carcinoma-derived cell line (IP-B12) as a new model of humoral hypercalcemia of malignancy and bone metastasis.
Journal Tumour Biol.
Abstract A cloned cell line (IP-B12) derived from a transplantable rat pulmonary carcinoma (IP), of which neoplastic cells produce parathyroid hormone-related protein (PTHrP), was established. Tumors induced in syngeneic F344 rats by intraperitoneal injection of IP-B12 cells had features of pulmonary adenocarcinomas, consisting of neoplastic cells immunopositive to PTHrP. The IP-B12 tumor-bearing rats developed severe emaciation and hypercalcemia, with a marked elevation of plasma PTHrP level; there was an increase in osteoclastic areas of the femur and calcium depositions in systemic organs, indicating progression to humoral hypercalcemia of malignancy (HHM) in the tumor-bearing rats. In addition, the injection of IP-B12 cells into the left cardiac ventricle of syngeneic rats resulted in osteolytic skeletal metastases in the long bones and vertebrae. In the metastatic lesions, histologically, neoplastic cells showed an immunopositive reaction to PTHrP, and a prominent osteoclastic activity was seen; bone lesions, including osteolysis, fracture, and nerve compression as well as replacement of bone marrow cells by proliferated tumor cells were similar to those reported in human cancer patients with bone metastases. IP-B12 is a new animal model for HHM and osteolytic bone metastases, and will become a useful tool for studies on the pathogenesis and therapeutic strategies for such conditions.
Volume 24(2)
Pages 70-6
Published 2003-3
DOI 10.1159/000071079
PII 71079
PMID 12853701
MeSH Animals Bone Neoplasms / blood Bone Neoplasms / secondary* Disease Models, Animal Humans Hypercalcemia / blood Hypercalcemia / etiology* Hypercalcemia / pathology Lung Neoplasms / blood Lung Neoplasms / pathology* Male Neoplasm Transplantation Rats Rats, Inbred F344 Tumor Cells, Cultured*
IF 3.65
Times Cited 2