Novel shear flow assay provides evidence for non-linear modulation of cancer invasion

Kingston University, Digital Imaging Research Centre, Penrhyn Rd, Kingston-upon-Thames KT1 2EE, UK.
Frontiers in Bioscience (Impact Factor: 3.52). 02/2009; 14(8):3085-93. DOI: 10.2735/3437
Source: PubMed


Cancer is a frequent disease in western countries and there is no effective treatment for metastasis, the main cause of death in cancer patients. The situation can be improved by a better understanding of the cancer invasion process. In order to reveal new aspects of this dynamic process, we developed a novel direct viewing cancer cell invasion assay with shear flow in vitro. This assay comprised of a custom-made flow chamber, specially developed cell labelling, high-resolution wide-field microscopy and image-processing-based quantitation. We applied this assay to metastatic rat sarcoma cells which invaded monolayers of rat endothelial cells. Our findings showed that after adhesion, the sarcoma cells initially invaded significantly faster under flow conditions compared to situations without shear stress. Later, however, the rate of invasion under flow decreased and the sarcoma cells without shear stress achieved significantly higher levels of invasion. Our observations thus revealed the non-linear modulation of a cancer cell invasion process by shear flow, demonstrating that cancer cells can respond to flow by enhancement of invasiveness similarly to white blood cells.

Download full-text


Available from: Deborah Aubyn, Oct 06, 2015
1 Follower
47 Reads
  • European Journal of Cancer 03/1998; 34(2):214-21. DOI:10.1016/S0959-8049(97)10129-0 · 5.42 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The most life-threatening aspect of cancer is the undetected spread of tumor cells throughout the body. Improved understanding of how these cells invade tissues is leading to new treatments.
    Scientific American 03/1992; 266(2):54-9, 62-3. DOI:10.1038/scientificamerican0292-54 · 1.07 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The process of metastasis is not random. Rather, it consists of a series of linked, sequential steps that must be completed by tumor cells if a metastasis is to develop. Although some of the steps in this process contain stochastic elements, as a whole, metastasis favors the survival and growth of a few subpopulations of cells that preexist within the parent neoplasm. Moreover, metastases can have a clonal origin, and different metastases can originate from the proliferation of single cells. The outcome of metastasis depends on the interaction of metastatic cells with different organ environments. Organ-specific metastases have been demonstrated in a variety of experimental tumor systems. Moreover, we have found tumor growth that is specific to a particular site within one organ. Whether the same conclusions can be reached for human cancers remained unanswered until very recently. Studies from our laboratory and from others have shown that the implantation of human cancer cells derived from surgical specimens into correct anatomical sites of nude mice can provide a suitable model of metastasis of human tumors. Clonal analysis of a human renal carcinoma, colon carcinomas, and melanomas has revealed that these tumors are indeed heterogeneous for metastatic properties, an observation made only after orthotopic implantation. Thus, growth in the environment of specific organs can be selective and the environment per se influences this process. While it is clear that vascularity and local immunity can facilitate or retard tumor growth, we have concentrated on understanding how damage to an organ and the subsequent repair process can facilitate tumor cell proliferation. Accelerated growth of human colon cancer cells was found in hepatectomized nude mice, whereas accelerated growth of human renal cancer cells was found in nephrectomized nude mice. These data suggest that systemic physiological signals can be recognized by neoplastic cells presumably by mechanisms similar to those shared by their normal cell counterparts. In summary, the critical factors that regulate metastasis are the intrinsic properties of metastatic cells and host factors involved in homeostasis. The recent increase in our understanding of metastasis should provide important leads for developing more effective approaches to the treatment of disseminated cancer.
    Cancer Research 11/1990; 50(19):6130-8. · 9.33 Impact Factor
Show more