Abstract
In order to grow, tumors need to induce supportive alterations in the tumor-bearing organ, by us named tumor instructed normal tissue (TINT) changes. We now examined if the nature and magnitude of these responses were related to tumor size and aggressiveness. Three different Dunning rat prostate tumor cells were implanted into the prostate of immune-competent rats; 1) fast growing and metastatic MatLyLu tumor cells 2) fast growing and poorly metastatic AT-1 tumor cells, and 3) slow growing and non-metastatic G tumor cells. All tumor types induced increases in macrophage, mast cell and vascular densities and in vascular cell-proliferation in the tumor-bearing prostate lobe compared to controls. These increases occurred in parallel with tumor growth. The most pronounced and rapid responses were seen in the prostate tissue surrounding MatLyLu tumors. They were, also when small, particularly effective in attracting macrophages and stimulating growth of not only micro-vessels but also small arteries and veins compared to the less aggressive AT-1 and G tumors. The nature and magnitude of tumor-induced changes in the tumor-bearing organ are related to tumor size but also to tumor aggressiveness. These findings, supported by previous observation in patient samples, suggest that one additional way to evaluate prostate tumor aggressiveness could be to monitor its effect on adjacent tissues.
Highlights
Prostate cancer is a common, generally multifocal, disease with variable behavior ranging from harmless to lethal
Vehicle (RPMI medium) was injected into the prostate of immune competent rats to examine the response to the injection per se, heat-killed AT-1 or G tumor cells were injected to study the immunogenic response to tumor cell debris
Macrophage and mast cell densities at 10 (RPMI and heat-killed AT-1) and 42 days after injection were analyzed in the different control prostates and in intact prostate tissue
Summary
Prostate cancer is a common, generally multifocal, disease with variable behavior ranging from harmless to lethal. Many prostate cancers are difficult to detect by imaging. Tissue biopsies can not be safely guided towards tumors. To circumvent this problem multiple needle biopsies are taken from the organ, but biopsies are small and sample less than 1% of the prostate volume. In most men with raised serum PSA cancer is not found in the biopsies [2,3,4,5]. This could be a true or a false negative result. When cancer is detected, it is uncertain whether or not the most malignant foci have been sampled. Additional ways to improve prostate cancer diagnostics are needed [2, 3, 5, 6]
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