The University of Osaka · Medicine
Professor Toshiyuki Yoneda's research lab focuses on the molecular mechanisms underlying cancer metastasis, particularly the bone-seeking behavior of breast cancer cells and the role of the tumor microenvironment in promoting metastatic progression. The lab investigates key biological processes such as tumor cell invasion, osteoclastic bone resorption, and the influence of acidic extracellular microenvironments driven by V-ATPase activity. Using in vivo models and in vitro systems, the lab explores therapeutic strategies targeting metastasis, including bisphosphonates and MMP inhibitors, with an emphasis on optimizing combination therapies for bone and visceral metastases. Their work bridges basic cancer biology with translational applications to improve treatment outcomes.
Figures are computed from collected data and may differ slightly.
Breast cancer has a predilection for spreading to bone. The mechanism of preferential metastasis of breast cancer to bone is unknown. We hypothesize that breast cancer cells that develop bone metastases have the capacity to facilitate their colonization in bone. To examine this hypothesis, we established bone-seeking (MDA-231BO) and brain-seeking (MDA-231BR) clones of the human breast cancer cell line MDA-MB-231 by repeated sequential passages in nude mice and in vitro of metastatic cells obtain
Multiple steps are involved in the metastasis of cancer cells from primary sites to distant organs. These steps should be considered in the design of pharmacologic approaches to prevent or inhibit the metastatic process. In the present study, we have compared the effects of inhibiting several steps involved in the bone metastatic process individually with inhibition of both together. The steps we chose were matrix metalloproteinase (MMP) secretion, likely involved in tumor cell invasion, and ost
These results suggest that BP has beneficial effects on bone metastasis of breast carcinoma and is more effective when combined with anticancer agents. They also suggest that the animal models of bone metastasis described here allow us to design optimized regimen of BP administration for the treatment of breast carcinoma patients with bone and visceral metastases.
Accumulating evidence indicates that the acidic microenvironments critically influence malignant behaviors of cancer including invasiveness, metastasis, and chemoresistance. Because the vacuolar-type H(+)-ATPase (V-ATPase) has been shown to cause extracellular acidification by pumping protons, we studied the role of V-ATPase in distant metastasis. Real-time PCR analysis revealed that the high-metastatic B16-F10 melanoma cells strongly expressed the a3 isoform V-ATPase compared to the low-metasta
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