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Plasma membrane damage induced in various cell targets by hematoporphyrin (HPD) photodynamic therapy (PDT) could modify cancer cell adhesiveness, an important parameter in cancer metastasis. We investigated the effect of HPD or HPD incubation followed by argon laser light on the adhesiveness of progressive (PROb) or regressive (REGb) cancer cells of the same colonic origin but with a different in vivo metastatic potential. Adhesiveness was studied on plastic or endothelial cell monolayers (ECM). In the absence of treatment, both PROb and REGb cells adhered better on plastic than on ECM. HPD alone or HPD-PDT induced toxicity proportional to the HPD dose. HPD-PDT increased the adhesiveness rate of both cell lines on plastic and decreased it on ECM. HPD-PDT of ECM increased adhesiveness, but only at HPD doses causing at least 50% cell death. With HPD treatment alone or HPD-PDT of culture media, there was no significant decrease in cell adhesiveness to ECM. We also studied the effect of HPD or HPD incubation followed by argon laser light on the metastatic potential of cancer cells, which was decreased for PROb with HPD alone or HPD-PDT. Decreased adhesiveness of colonic cancer cells to ECM after HPD-PDT was thus correlated with decreased metastatic potential. REGb cells did not acquire a progressive phenotype either in vitro or in vivo after HPD-PDT.

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Background. Photodynamic therapy (PDT) mediated by hematoporphyrin derivative (HPD) is a new treatment for cancers of small volume undergoing Phase II or III clinical trials in various medical fields. However, there is a lack of prognostic criteria of efficacy as in other cancer treatment. Methods. Cell DNA content or cell kinetics throughout the cell cycle were analyzed by flow cytometry and propidium iodide staining before and after HPD‐PDT in 33 patients with Tis or T1 cancers of the gastrointestinal tract. The authors compared results in near‐diploid cancers with those obtained in normal corresponding tissue. Results. Complete local tumor destruction and negative histologic findings (complete response [CR]) were observed in 17 of 33 patients during a period averaging 15.7 months. Flow cytometry DNA analysis was feasible in 32 patients. Aneuploidy, found in 15 of the 32 indicated a poor prognosis because 5 of 15 patients with aneuploid tumors were classified as having CR, compared with 12 of 17 patients with near‐diploid tumors (P < 0.05). Changes in ploidy after PDT in 11 patients consisted of a reduction in the number of aneuploid peaks in 8 patients and the appearance of one aneuploid peak in 3 patients. Percentages of cells in SG2M phase in near‐diploid tumors differed from those observed in control subjects for adenocarcinomas, and there was no significant decrease after HPD‐PDT. There was no correlation between the decrease of SG2M cells and the response to HPD‐PDT. Conclusion. Results obtained with PDT in this series of patients confirm previously published findings. Changes occurring in the ploidy of PDT‐treated patients demonstrate that PDT acts directly on cancer cells in humans and not only on tumor vasculature. However, response to PDT varies from one cell population to another. The appearance of aneuploid populations after PDT suggests that destruction of sensitive cell populations allows the growth of aneuploid clones that initially are not detectable by flow cytometry.

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