Year: 2012
Type: dissertation
Abstract: Mast cells (MCs) release a variety of biologically potent mediators exerting their effects either locally or systemically.Many of these are preformed mediators stored in the cytoplasmic granules, while others are produced de novo upon MC activation.During the last 15 years, human MCs have also been recognized as a source of cytokines and they can express a wide range of cell surface molecules.All these molecules may participate in carcinoma development through matrix degradation, immunomodulation, angiogenesis or tumor cell proliferation.In this work, the possible role of MC mediators histamine, heparin, tryptase, chymase, TNF-α and other TNF superfamily ligands CD30L and CD40L was investigated in squamous (SCC) and/or basal cell (BCC) carcinomas.The expression of these factors in SCC and BCC and the possible involvement of mediators in the growth, migration and adherence of uterine cervical SCC cells (SiHa and ME-180 cell lines) were studied by using histochemical and cell culture techniques.The results show that in superficial spreading BCC, the number of tryptase-and chymasepositive MCs (MCTC cells) is increased, possibly as a consequence of Kit receptor activation by the stem cell factor.Even though tryptase was apparently fully active in the BCC lesion, chymase was partially inactivated possibly due to action of α1-proteinase inhibitor and α1antichymotrypsin localized to mast cells.However, residual chymase activity may still cause matrix degradation and other effects in the lesion.In addition, MCs express CD30L and TNF-α, but not substantially CD40L, in the BCC lesion.The counterpart receptors of all these ligands are present in the lesional epidermis or dermis, but basal buds were negative for TNFRI and CD40.In uterine cervical SCC specimens, MCTC cells were detected in substantial numbers in the peritumoral stroma, and in vitro especially chymase was capable of detaching viable and growing cervical SCC cells from substratum.The amount of chymase inhibitor SCCA-2 in cervix cancer cells is low as only weak immunopositivity for this antigen was found.In contrast to normal keratinocytes where TNF-α and histamine together had a profound growth-inhibitory and cytolytic effect, these mediators did not affect markedly the cervical SCC cells.Based on these results, chymase may release viable SCC cells from a tumor leading to spreading of SCC.In addition, SCC cells may have lost their responsivity to the cytolytic action of TNF-α and histamine, a conclusion based partly on the result that SiHa and ME-180 cells and cervix SCC expressed only relatively low levels of TNFRI and II.In the BCC lesion, significant changes were found in MCTC cells pointing to an intimate involvement in pathogenesis.Decreased chymase activity may not be able to degrade TNF-α or cleave the malignant epithelium away, and the lack of CD40L in MCs may result in inefficient antitumoral response.
Author: Nicolae-Costin Diaconu
Language: English
Topic: Mast cells and histamine
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Funder: Itä-Suomen Yliopisto
OpenAlex ID: W3097885731