Prostatic tumor (R3327) skeletal metastasis

Abstract

Male Copenhagen rats were inoculated with monodispersed R3327-MatLyLu prostate tumor cells via the tail vein under concomitant temporal occlusion of the inferior vena cava to develop an animal model for skeletal metastasis of prostate cancer. This procedure reproducibly resulted in metastatic tumor growth in the lumbar region of the vertebral column. Microscopically, tumor growth became visible in the fifth and sixth lumbar vertebrae within 4 days after inoculation. Clinical signs of nerve function disablement (hind leg paresis and paralysis) followed within 14 days of such a procedure. Cell culture technique confirmed the presence of a viable, proliferating tumor cell population within the spinal canal of the fifth and sixth lumbar vertebrae. Histologically, a clear response of osteoclastic and concomitant osteoblastic activities was observed in the lumbar spinal column. In the serum, a transient phase of hypercalcemia could be demonstrated. The development of skeletal metastases in these animals was not reflected by significant alteration in serum levels of acid phosphatase, prostatic-specific antigen, or osteocalcin. These observations support the concept of the vertebral venous plexus being involved in the dissemination of prostate tumor cells. The surgical procedures described permit experimental investigations of bone metastasis of prostatic cancer.

The Dunning model

“…There are differing reports regarding the expression of prostate cancer markers in the Dunning model. In 1990, Newhall et al reported that none of five Dunning lines examined expressed detectable levels of prostatic acid phosphatase (PAP) or prostate-specific antigen (PSA) [14]. However, in 1993, Garde et al reported that several sublines examined expressed PSA, PAP and prostatic inhibin peptide (PIP) [15].…”

Skeletal metastasis of prostate adenocarcinoma in rats: Morphometric analysis and role of parathyroid hormone-related protein

“…The MATLyLu subline is a rapidly growing, androgen-independent, highly metastatic, poorly differentiated adenocarcinoma cell line that has been used in a syngeneic rat model for the study of skeletal metastases [33,34]. Injection of neoplastic cells into the left cardiac ventricle leads to widespread metastasis to bone [13,34], while injection of MATLyLu cells in the tail vein under temporal occlusion of the posterior vena cava results in colonization of lumbar vertebrae [35,36]. In the intracardiac injection model, metastatic cells also have a particular affinity for lumbar vertebrae, leading to focal compression of the spinal cord and development of posterior paralysis; however, an in depth characterization of the osteoblastic vs. osteolytic nature of metastases in this model has not been reported [13,34].…”

Chemically modified non-antimicrobial tetracyclines are multifunctional drugs against advanced cancers☆

“…We observed extensive bone metastasis in a rat model of prostate cancer, the Dunning MAT Ly Lu, after intravenous injection of tumor cells while clamping the vena cava [27,28] in the male Copenhagen strain. This resulted in forced invasion of tumor cells into the lumbar vertebral venous plexus (Batson’s plexus) and extensive vertebral metastasis [29,30]. In addition, the Dunning MAT LyLu tumors also spread to lungs and form extensive lung metastasis [31].…”