Photofrin accumulation in malignant and host cell populations of a murine fibrosarcoma.
Photofrin (25 mg/kg) was administered to the FsaR fibrosarcoma-bearing mice (either syngeneic or severe combined immunodeficient [SCID]) and the tumors were excised 24 h later. The photosensitizer content in the cells dissociated from tumor tissue was analyzed using flow cytometry. Staining the cell suspensions with the monoclonal antibodies against specific membrane markers served to identify the malignant cells and various types of host immune cells infiltrating the tumor. Photofrin content was also examined in the cells from normal tissues of the tumor-bearing mice (spleen, heart muscle, peritoneal macrophages). The results show a marked heterogeneity in the Photofrin cellular content of FsaR tumor, particularly within the population of tumor-associated macrophages (TAM). The Photofrin levels in some TAM were lower or similar to those in the malignant cells. In contrast, a subpopulation of TAM accumulated very high levels of the photosensitizer, which exceeded by far the levels found in the other tumor cell populations. This TAM fraction was characterized by particularly high expression of interleukin-2 receptors and increased cell size and granularity when compared to the other TAM, which suggests that these macrophages are in the activated state. Their average Photofrin content was almost 13 times higher than in the malignant cells. The lowest photosensitizer levels in the tumor were found in tumor-infiltrating leukocytes other than TAM. In FsaR tumors growing in SCID mice, the pattern of Photofrin distribution in TAM and other cellular populations was similar to that found in tumors growing in syngeneic mice.(ABSTRACT TRUNCATED AT 250 WORDS)
Korbelik
M
M
Cancer Imaging, B.C. Cancer Agency, Vancouver, Canada.
Krosl
G
G
D000818:Animals; D005260:Female; D005354:Fibrosarcoma / Q000378:metabolism* / Q000473:pathology; D017324:Hematoporphyrin Derivative / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D013050:Spectrometry, Fluorescence
D017324:Hematoporphyrin Derivative