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Identification of a novel cell population in nonhealing wounds in tumors
R A Gatenby1, D D Taylor, D J Ellison
1Department of Diagnostic Imaging, University of Arizona Medical Center, Tucson 85724.
Abstract:
We have explored wound healing in tumors as a possible model for tumor-host interaction. This work demonstrated tumor wound healing failure to be the result of intense inhibition of fibroblasts although the tumor cells did not appear to be the direct source of the inhibitors. The inflammatory infiltrate found in tumor wounds was then examined for possible sources of the observed fibroblast suppression. Although the tumor wound infiltrate contains cell populations similar to a normal wound infiltrate, it also contains a large, vacuolated, nonadherent, phagocytic mononuclear cell which has morphologic and cytochemical characteristics of a lipid-laden macrophage. However, the cell also proliferates under normal culture conditions and has an immunophenotype more characteristic of lymphocytes than those of macrophages with striking expression of the CD8 surface antigen. Conditioned media from this cell population markedly inhibit fibroblast proliferation suggesting it is the source of fibroblast inhibitors within the tumor wound. Mechanical dissociation of non-wounded tumors yielded evidence that the tumor wound cell is normally present in small numbers within the tumor.
Insights
Tumor wound healing fails due to fibroblast inhibition by unique mononuclear cells. These cells, present in tumor infiltrates, suppress fibroblast proliferation, impacting tumor-host interactions.
Area of Science:
- Oncology
- Immunology
- Cell Biology
Background:
- Tumor wound healing failure suggests complex tumor-host interactions.
- Fibroblast inhibition is a key factor in impaired wound healing within tumors.
Purpose of the Study:
- To investigate the source of fibroblast inhibitors in tumor wounds.
- To characterize the unique mononuclear cells found in tumor inflammatory infiltrates.
Main Methods:
- Analysis of inflammatory infiltrate in tumor wounds.
- Morphologic, cytochemical, and immunophenotypic characterization of mononuclear cells.
- Assessment of conditioned media from these cells on fibroblast proliferation.
Main Results:
- Tumor wound healing failure is linked to potent fibroblast inhibitors.
- A novel mononuclear cell population, resembling lipid-laden macrophages but with lymphocyte-like immunophenotype (CD8+), was identified.
- Conditioned media from this cell population significantly inhibited fibroblast proliferation.
- These cells are present in small numbers in non-wounded tumors.
Conclusions:
- The identified mononuclear cell is the likely source of fibroblast inhibitors in tumor wounds.
- This cell's unique characteristics challenge traditional macrophage/lymphocyte classifications.
- Understanding this cell's role is crucial for novel therapeutic strategies targeting tumor-host interactions.