The international team led by Dr. Jacqui McGovern, from the Centre for Biomedical Technologies, used tissue engineering and regenerative medicine principles to create primary tumors with their microenvironment and humanized bone as a metastatic site for prostate cancer cells to spread to.
They used two types of prostate cancer cell lines—one that is sensitive to male hormones (androgens) (LNCaP) and the other, a more aggressive type (PC-3), which is non-sensitive to androgens.
“We found that the tumor microenvironment influences the spread of cancer to bone and visceral organs in a manner specific to the cells with low (LNCaP) and high (PC-3) metastatic potential,” said Dr. McGovern, a member of the QUT School of Biomedical Sciences.
“Our aim was to study the interaction of cancer cells and the bone metastatic microenvironment to better understand the complex interactions between them,” Dr. McGovern said.
“We know the primary tumor’s microenvironment is an agent for prostate cancer development, growth, progress and metastasis but because the tumor microenvironment is complex and multifaceted it is difficult to delineate the roles of its specific components.”
Dr. McGovern said the team engineered primary prostate tumors in a mouse model using two critical prostate cancer tumor microenvironment cell types—fibroblasts and microvascular endothelial cells—which have been implicated in directly contributing to prostate cancer metastasis.
“Both the LNCaP and PC-3-derived primary prostate tumors containing these critical cells type developed and metastasized over a 10–11-week period,” she said.
“Interestingly, the humanized tumor microenvironment showed a trend to decrease metastasis of the more aggressive PC-3 cells to humanized bone but did not influence metastasis to the mouse bones or visceral organs.
“In contrast, the LNCaP primary tumor microenvironment actually enhanced tumor growth and bone metastasis.
“These results uncover a potential new role of the tumor microenvironment in prostate cancer’s tendency to metastasise to bone which warrants further investigation.
“However, we are only at the beginning of exploring how the signaling processes between cancer cells and the microenvironment can structure tumor cell communities.”
“A humanized orthotopic tumor microenvironment alters the bone metastatic tropism of prostate cancer cells” is published Nature Communications Biology.