Histo-cytological characterization of human breast carcinoma cells cultured on pigskin and plastic substrates

Thesis

Breast cancer remains the leading cause of mortality among western women and its incidence is increasing (Tjandra and McKenzie. 1988; Allred eta/., 1990). Although several different and effective therapeutic treatments for breast cancer are used; all suffer to some extent from lack of specificity. At present, chemotherapeutical treatment of cancer is done very much on a "touch wood" basis as far as the drug mixture and dose is concerned. Currently breast cancer cells appear to be one of the most difficult cancers to establish in culture (Fogh, 1975; Hainsworth and Garson, 1990). The fact that cancers are classified as identical according to their histopathological characteristics but are nonetheless highly individual in their drug sensitivities, poses a major clinical problem (Vescio et aI., 1987). Ample documentation exists confirming that most cancers consist of subpopulations of tumour cells which differ with regard to numerous properties. Subpopulations of single tumours often have differential drug sensitivities. The growth characteristics and sensitivity to chemotherapeutic agents of individual tumour subpopulations can also be influenced by the presence of other subpopulations of the same tumour (Miller et aI., 1981). There is currently no way to predict clinical outcome of chemotherapy for individual patients. There is also no optimum assay to screen for new human anticancer agents, especially for solid tumours, which presents a second problem . Many attempts have been made to develop in vitro drug-sensitivity tests for individual cancer patients about to undergo chemotherapy and to screen for new anticancer agents (Vescio et aI., 1987). However, most of these attempts have suffered in one form or another . from their inability to support growth of human tumours such that they reflect the in vivo situation. In many instances plating of dissociated tumour cells in soft agar and monolayer cultures does not allow the growth of tumour cells (Vasiliev and Gelfland, 1981). Furthermore, Schor et al. (1982) stressed that, "there is a growing awareness that cell migratory behaviour in vitro should be examined on biologically relevant macromolecular matrices, rather than on the artificial surfaces commonly used in such studies. Collagen is a major constituent of the extracellular matrix in vivo." Often, when some tumour cells do grow under cu lture conditions, other cell types present in the original tumour probably have not grown (Vescio et a/., 1987). Overgrowth by fibroblasts is often a problem, especially in long term cultures (Emoto et aI., 1992). Since it has been shown that interactions between cell types can alter their drug sensitivities, it is critical that the cell types present in the original tumour also be present in the assay (Vescio, et a/.,1987; Jung et aI., 1991). An assay system representing the original tumour for individual cancer patients who will respond differently, according to his or her own metabolic capabilities, is therefore needed to determine the sensitivity of the cancer cells to different drugs as well as combinations of drug types. The aim should also be focussed on any kind of short-term assay which will improve the ability of scientists to do chemical testing (Klausner, 1987; Vescio et a/., 1987).