A humanized orthotopic tumor microenvironment alters the bone metastatic tropism of prostate cancer cells

Prostate cancer (PCa) is the second most commonly diagnosed cancer in men, and bone is the most frequent site of metastasis. The tumor microenvironment (TME) impacts tumor growth and metastasis, yet the role of the TME in PCa metastasis to bone is not fully understood. We used a tissue-engineered xenograft approach in NOD-scid IL2R gamma(null) (NSG) mice to incorporate two levels of humanization; the primary tumor and TME, and the secondary metastatic bone organ. Bioluminescent imaging, histology, and immunohistochemistry were used to study metastasis of human PC-3 and LNCaP PCa cells from the prostate to tissue-engineered bone. Here we show pre-seeding scaffolds with human osteoblasts increases the human cellular and extracellular matrix content of bone constructs, compared to unseeded scaffolds. The humanized prostate TME showed a trend to decrease metastasis of PC-3 PCa cells to the tissue-engineered bone, but did not affect the metastatic potential of PCa cells to the endogenous murine bones or organs. On the other hand, the humanized TME enhanced LNCaP tumor growth and metastasis to humanized and murine bone. Together this demonstrates the importance of the TME in PCa bone tropism, although further investigations are needed to delineate specific roles of the TME components in this context. McGovern et al. establish an orthotopic, humanized prostate cancer model to study bone metastasis. The authors demonstrate that a humanized tumor microenvironment (TME) influences the metastatic spread of cancer cells to tissue-engineered bone, highlighting the importance of the TME in prostate cancer metastasis to bone.

Automated summary

In this study, pre-seeding scaffolds with human osteoblasts increased the human cellular and extracellular matrix content of bone constructs, while the humanized prostate TME showed a trend to decrease metastasis of PC-3 cells to tissue-engineered bone. On the other hand, the humanized TME enhanced LNCaP tumor growth and metastasis to both humanized and murine bone. This emphasizes the importance of the TME in prostate cancer metastasis to bone.