Steps of the metastatic process. Metastasis is characterized by a series of sequential steps: primary tumor formation, recruitment of blood vessels through angiogenesis, cancer cell invasion of local tissue, and entry into dispersal corridors such as blood vessels. Disseminated cells travel through the circulation and upon reaching a suitable secondary site such as the bone, extravasate from the blood vessels, and colonize to form bone metastases (modified from Servier Medical Art by Servier licensed under CC BY 3.0.).
Optimal foraging of prostate cancer cells. The optimal foraging strategy employed by a cancer cell is influenced by three interacting factors: available resources (e.g., oxygen, glucose), predation risk (e.g., cytotoxic T cells, M1 macrophages), and movement ability (e.g., mesenchymal phenotype, permissible ECM).
Prostate cancer resource patches and dispersal corridors. A, Primary prostate tumor from prostate cancer patient radical prostatectomy (a, lymphovascular vessel; b, nerve; c, intraductal carcinoma; d, stromal infiltration). B, Prostate cancer resource patches: colored regions represent patches within the primary tumor and depict spatial heterogeneity at single moment in time. Variations in color represent variations in patch characteristics (i.e., resource and predation risk). Importantly, although not depicted, patch geography and characteristics change over time. C, Dispersal corridors including blood vessels (red and maroon), lymph vessels (green), and nerves (orange) intersect primary tumor patches and provide a route for long-distance dissemination out of the primary tumor habitat. (H&E; scale bar, 300 μm; image courtesy of Dr. Tamara Lotan, Johns Hopkins University)
Inefficiency of prostate cancer metastasis. Of the cells that disseminate from the primary tumor (detected as CTCs from the venous circulation), very few become bone DTCs and even fewer eventually form clinical metastases. The inefficiency of each of step compounds with progression along the metastatic process.