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Matrix metalloproteinase (MMP)-2 and MMP-9 Expression in Tumor Infiltrating CD3 Lymphocytes From Women With Endometrial Cancer
  1. Marcin Jedryka, MD, PhD*,
  2. Agnieszka Chrobak, PhD,
  3. Anna Chelmonska-Soyta, PhD,
  4. Daria Gawron, MSc,
  5. Alicja Halbersztadt, MD, PhD,
  6. Andrzej Wojnar, MD, PhD§ and
  7. Jan Kornafel, MD, PhD*
  1. *Department of Gynaecological Oncology, Wroclaw Medical University;
  2. Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Science;
  3. Faculty of Biotechnology, University of Wroclaw; and
  4. §Department of Pathomorphology, Lower Silesian Centre of Oncology, Wroclaw, Poland.
  1. Address correspondence and reprint requests to Marcin Jedryka, MD, PhD, Department of Gynaecological Oncology, Wroclaw Medical University, Pl Hirszfelda 12, 53-314 Wroclaw, Poland. E-mail: mjedryka{at}interia.pl.

Abstract

Objective In this study, we hypothesized that not only endothelial malignant cells but also lymphocytes infiltrating tumor epithelium, in patients with endometrial cancer, could be an important source of the gelatinases (matrix metalloproteinase [MMP]-2 and MMP-9) extensive production, which in turn, may facilitate tumor cells infiltration and progression due to the extracellular matrix degradation.

Materials and Methods First, we isolated lymphocytes from the endometrial carcinoma samples taken from 41 patients who were operated on and from healthy endometrial tissue taken of the same patients after histological verification. Then, we detected the level of CD3-positive cells in endometrial tissues by flow cytometry. Simultaneously, we studied the messenger RNA expression of MMP-2 and MMP-9 in the isolated cells from malignant and unchanged endometrial tissues. Using immunohistochemistry, we compared the protein expression of MMP-2, MMP-9, and CD3 in the studied samples.

Results We showed the enhanced abundance of CD3 lymphocytes both by flow cytometry and immunohistochemistry in the samples from malignant tissues. The expression of MMP-9 in the endometrial carcinoma was increased significantly at the protein level but not at the messenger RNA level. We could not observe any differences concerning MMP-2 expression in both methods of detection.

Conclusions CD-3 lymphocytes significantly infiltrate endometrial cancer tissue, but they do not seem to be the source of enhanced metalloproteinases 2 and 9 expression in the tumor environment. Still, owing to the immunohistochemistry staining, we could show the significant increase of MMP-9 protein in the very close vicinity of tumor-infiltrating CD3 lymphocytes. Could it be the result of CD3 lymphocyte action, or is it just the imperfection of the detecting method we used? This remains unclear. Further studies explaining the role of tumor infiltrating lymphocytes in mediating the endometrial cancer milieu are needed.

  • Endometrial cancer
  • CD3 lymphocytes
  • MMP-2
  • MMP-9

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Footnotes

  • The authors declare no conflict of interest.

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