Prostate cancer is the second leading cause of cancer-related death in men. A typical feature of this disease is its ability to metastasize to bone. It is mainly osteosclerotic, and is caused by a relative excess of osteoblast activity, leading to an abnormal bone formation. Bone metastases are the result of a complex series of steps that are not yet fully understood and depend on dynamic crosstalk between metastatic cancer cells, cellular components of the bone marrow microenvironment, and bone matrix (osteoblasts and osteoclasts). Prostate cancer cells from primary tissue undergo an epithelial-mesenchymal transition to disseminate and acquire a bone-like phenotype to metastasize in bone tissue. This review discusses the biological processes and the molecules involved in the progression of bone metastases. Here we focus on the routes of osteoblast differentiation and activation, the crosstalk between bone cells and tumor cells, and the molecules involved in these processes that are expressed by both osteoblasts and tumor cells. Furthermore, this review deals with the recently elucidated role of osteoclasts in prostate cancer bone metastases. Certainly, to better understand the underlying mechanisms of bone metastasis and so improve targeted bone therapies, further studies are warranted to shed light on the probable role of the premetastatic niche and the involvement of cancer stem cells. Cancer 2010;116:1406-18. V C 2010 American Cancer Society.KEYWORDS: osteoblasts, osteoclasts, prostate cancer, bone, metastasization.Solid tumors, such as breast and prostate cancer, have an affinity to metastasize to bone, causing osteolysis and abnormal bone formation. Bone metastasis starts with the tropism of cancer cells to the bone through specific migratory and invasive processes. Once in the bone marrow, metastatic cells are able to survive and grow. Here, they actively interact with bone marrow stem cells and hematopoietic progenitors in the so-called metastatic niche, where they acquire a bonelike phenotype. This leads to the formation of bone lesions (lytic or osteoblastic), obtained through reciprocal paracrine amplification and cell-to-cell communication with bone cells. The complex molecular pathogenesis mechanisms of bone metastasis offer several potential targets for prevention and therapy.Prostate cancer is the second leading cause of cancer-related death in men, and a typical feature of this disease is its ability to metastasize to bone. Indeed, it has been estimated that >80% of men who die from prostate cancer develop bone metastases.1,2 Although most bone metastases from prostate cancer have been classified as osteoblastic, based on the radiographic appearance of lesions, it is clear that bone resorption and bone formation are dysregulated. 3-5The Metastatic Process: From Primary Tumor to Growth in Bone Tissue The first step in metastasization is the acquisition of motility and invasiveness; capabilities that are not compatible with normal tissue. Cancer cells must therefore shed many of their epithelial ch...

Purpose:The identification of new molecular markers for the early detection of colorectal cancer has become an important objective.We compared the sensitivity and specificity of free circulating DNA with that of the more conventional carcinoembryonic antigen (CEA) and evaluated the two markers in combination. Experimental Design: The study was carried out on 75 healthy donors and 75 colorectal cancer patients. Free DNA was determined in serum with quantitative PCR analysis. The diagnostic accuracy of each assay was calculated using receiver operating characteristic (ROC) curves. The diagnostic relevance of the two-marker combination was analyzed by the logistic regression model. Results: Median free DNA concentration was f5-fold higher in patients than in healthy donors (P < 0.001). The area under the ROC curve was 0.86, and when 12.5 ng/mL was used as cutoff, 81.3% sensitivity and 73.3% specificity were observed for the overall series. As CEA and free DNA provided independent diagnostic information, they were also considered in combination. ROC curve analysis of the combined CEA and free DNA algorithms showed a higher diagnostic capacity (area under the ROC curve, 0.92) than that of markers considered singly, with 84% sensitivity and 88% specificity. Conclusions: Free circulating DNA, especially when used in combination with CEA, represents a potentially useful tool for the diagnosis of early-stage colorectal cancer.

Our preliminary results confirm the usefulness of a multidisciplinary center for the management of patients with bone metastases, especially in terms of decreasing psychophysical suffering.

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Our data suggest that we are still a long way from being able to propose TIL + IL-2 treatment as an effective adjuvant therapy. However, the results confirm that the biological indicators examined could play an important role in modulating immunitary response against tumor cells.