Motility of tumor cells

Several lines of evidence indicate that active motility of tumor cells is required in the metastatic process. The metastatic potential of Dunning R-3327 rat prostatic adenocarcinoma sublines best correlates with their ability to move on a substrate, as assessed either by a visual grading system of time-lapse videomicroscopy, or by a computerized mathematical system using spatial temporal Fourier analysis (Mohler, 1993). Similarly, the high metastatic capacity of a v-fos-transfected rat fibrosarcoma cell line corre-... 

Farina, K. L., Wyckoff, J. B., Rivera, J., Lee, H., Segall, J. E., CondeeUs, J. S. and Jones, J. G. (1998). CeU motility of tumor cells visualized in Uving intact primary tumors using green fluorescent protein. Cancer Res. 58, 2528-2532. 

A second hypothesis to explain invasion proposes that the invasive potential of tumor cell gd ives from their Increased mobility and/or decreased adhesiveness. These two alterations would change the contact relationships of cells, permitting cells to invade surrounding tissues. However, since the increased motility of tumor cells appears to be random, not directional, their increased motility, per se, would not lead to invasion. In addition, many normal cells which are not invasive are quite motile. 

A factor known as scatter factor has been characterized which causes the break up and stimulates motility of epithelial cell clumps (Stoker et al., 1987). This factor is identical to hepatocyte growth factor and increases the rate of locomotion of several other cell types. Motility factors elaborated from tumor cells are considered to play an important role in metastasis (see later). Guidance of cells by the physical topography of the substratum is another factor that profoundly affects the behavior of cells. 

Collins CS, Hong J, Sapinoso L et al (2006) A small interfering RNA screen for modulators of tumor cell motility identifies MAP4K4 as a promigratory kinase. Proc Natl Acad Sci USA 103 3775-3780... 

Infection with Moloney murine leukemia virus of a lymphoma cell line in vitro resulted in the identification of a gene—Tiaml— that affects the invasive ability of tumor cells (Habets et al., 1994), and thus has the potential to affect also their metastatie behavior. Tiaml acts as an activator of racl, thereby influencing cytoskeletal architecture and cell motility (Collard et al., 1996). Although no clinical evidence has been reported to date of a role of Tiaml in... 

Silletti, S., Paku, S., and Raz, A., Autocrine motihty factor and the extracellular matrix. 11. Degradation or remodehng of substratum components directs the motile response of tumor cells. Int J. Cancer, 1998, 76 129-135. 

It is of interest that proteins termed motility factors (55-70 kD) are secreted by fetal cells and some tumor cells. These proteins act as autocrine factors and stimulate rapid movement by these cells. Motility factors induce the formation of cell processes that are packed with actin filaments and have an increased number of receptors for the matrix proteins laminin and fibronectin. The latter enhance the ability of the cells to bind to the extracellular matrix. Thus, it is likely that motility factors influence the organization of the cytoskeleton through changes taking place at the cell surface (reviewed by Warn and Dowrick, 1989). 

Intestinal pseudoobstruction is also part of paraneoplastic syndromes. The anti-/zu antibodies are useful to indicate this condition, as shown in bronchial small cell carcinoma [171], In pheochromocytoma [172] and carcinoid [173] neuromediators affecting small bowel motility are produced by the tumor cells. Intestinal pseudoobstruction has also been reported in neuroblastoma [174],... 

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