Pantel_CTC_Bone_marrow_microMetastasis_review_2008.pdf

CirculatingTumor Cells and BoneMarrowMicrometastasis CatherineAlix-Panabie res,1Sabine Riethdorf,2 and Klaus Pantel2 Abstract Sensitive immunocytochemical and molecular assays allow the detection of single circulating tumor cells (CTC) in the peripheral blood and disseminated tumor cells (DTC) in the bonemarrow as a common and easily accessible homing organ for cells released by epithelial tumors of various origins.The results obtained thus far have provided direct evidence that tumor cell dissemination starts already early during tumor development and progression. Tumor cells are frequently detected in the bloodandbonemarrowof cancer patientswithout clinical or evenhistopathologic signs of metastasis. The detection of DTC and CTC yields important prognostic information and might help to tailor systemic therapies to the individual needs of a cancer patient. In the present review,weprovide a critical reviewof (a) the currentmethods used for detectionof CTC/DTC and (b) data on the molecular characterization of CTC/DTC with a particular emphasis on tumor dor- mancy, cancer stem cell theory, and novel targets for biological therapies; and we pinpoint to (c) critical issues that need to be addressed to establish CTC/DTCmeasurements in clinical practice. Metastasis is the main cause of death in patients with solid epithelial tumors (i.e., carcinomas), which represent the majority of cancers in industrialized countries. Recently, Bernards and Weinberg (1) presented a new metastasis model in which the metastatic capacity is gained early during primary tumor development. Indeed, disseminated tumor cells (DTC) can be already detected at early stages of tumor progression in regional lymph nodes, peripheral blood, and in bone marrow of cancer patients using highly sensitive detection methods (2). Interestingly, bone marrow has emerged as a common homing organ for metastatic epithelial tumor cells, independent of the primary tumor site and the pattern of overt metastases (Table