Influence Of Microenvironment In Prostate Cancer Invasion And Metastasis

Cancer metastasis is established by not only cancer cells but also host tissue cells (seed and soil theory).14 For example, kidney cancer metastasizes mostly to the lung, breast and prostate cancer mostly to the bone, and colon cancer with high incidence to the liver (Fig. 2.3). The influence of organ environment on the growth, invasion and metastasis of

Lung Bone Liver

Fig. 2.3. 'Seed and soil' hypothesis (Paget, 1889).14

Lung Bone Liver

Fig. 2.3. 'Seed and soil' hypothesis (Paget, 1889).14

human renal cell carcinoma cells,8'10 bladder carcinoma cells15 and prostate carcinoma cells16'17 has been examined in animal models by injecting these cells at orthotopic sites. Renal and bladder cancer cells injected subcutaneously do not produce visceral or lymph node metastasis but, when injected at orthotopic sites, they produce lymph node or visceral metastasis, or both.8'15 Both prostate and bone (not lung or kidney) stromal cells are capable of LNCaP tumor growth in vivo by co-inoculating LNCaP cells with these organ-specific fibroblasts,17 on the speculation that LNCaP cell growth is regulated by growth factors such as bFGF and hepatocyte growth factor (HGF) secreted from organ-specific stromal cells.17,18 We have also demonstrated that PC3M prostate cancer cells established from liver metastasis of PC3 cells inoculated at orthotopic sites produce large tumors with lymph node metastasis and seminal vesicle invasion16 (Fig. 2.4). PC3M cells inoculated subcutis, however, produce only small tumors with no metastasis. Metastatic variant cells established by in vivo selection also showed high metastatic potential in vivo; high metastatic clones of human renal cancer, bladder cancer and prostate cancer show a higher incidence of invasion and metastasis than parental cells do.15-16,19 The highly metastatic renal cell carcinoma produces larger amounts of extracellular matrix degradative enzymes (MMP-2 or uPA) and angiogenetic factors (bFGF) than parental cells do. Moreover, the high metastatic variant of human bladder cancer cells produces larger amounts of epidermal growth factor (EGF)-receptor

Prostate Cancer: Science and Clinical Practice

Fig. 2.4. Orthotopic animal model of prostate cancer. (A) Inoculation of PC3M cells into the prostate of nude mice. P, prostate; R, rectum. (B) PC3M prostate cancer cells growing at orthotopic site (T) and lymph node metastasis (L).

than parental cells do.15 These findings suggest that the crucial factors for growth, invasion and metastasis are different for different cell types, and the capability for the production of these crucial factors could be induced by the micronenvir-onment at the tumor growing site, indicating that organ environment influences the growth and progression of human cancer. Factors related to organ-specific metastasis are shown in Table 2.1.

Table 2.1. Factors related to organ-specific metastasis.

Factors determined by tumor cell

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