Migrating and circulating breast carcinoma cells are within active phases of the cell cycle.

The emergence of blood-borne epithelial-derived tumour cells in breast cancer patients is generally supposed to be an indicator of cancer cell spread but only a very small percentage of these cells ultimately initiate metastases. In this study, we investigated the presence of the cell cycle marker Ki-67 in mammary tumour cells isolated from patients' blood and SKBR3 breast carcinoma cells by confocal laser scanning microscopy. We also compared the immunostaining patterns for Ki-67 of blood-borne tumour cells from the patients with actively migrating cells within a collagen matrix. Both circulating tumour cells and migrating SKBR3 cells were found to be in G1- or S-phase. These findings will have impact on adjuvant chemotherapy as circulating tumour cells that are within the active part of the cell cycle are highly susceptible to chemotherapeutic agents and therefore can be killed while they migrate to distant organs to build a metastasis.

Cancer cell motility--on the road from c-erbB-2 receptor steered signaling to actin reorganization.

Cell migration depends mainly on actin polymerization and intracellular organization, which are influenced by a vast variety of actin binding proteins (ABPs). Regulation of ABP activity is mediated by second messengers such as phosphoinositides and calcium. Signaling via these second messengers is initiated and regulated by membrane receptors, e.g., receptor tyrosine kinases (RTKs), and by adhesion molecule interactions (e.g., integrins and selectins) and focal adhesion kinases. A major role in steering second-messenger signaling and thus in actin cytoskeleton reorganization and motility of cancer cells is played by the RTK c-erbB-2. This occurs through a number of signaling pathways which involve mainly enzymes, e.g., phospholipase Cgamma1 and GTPases, which modify signaling molecules. Furthermore large multiprotein complexes including actin-related protein 2/3, Wiskott-Aldrich syndrome protein, profilin, and capping protein among others play an important role in regulating actin reorganization. The complex picture of the mode of actin reorganization, which is involved in tumor cell migration, is slowly emerging from the mists of cellular signaling pathways, but this is still by no means a clear view.