Upregulation of tissue kallikrein, kinin B1 receptor, and kinin B2 receptor in mast and giant cells infiltrating oesophageal squamous cell carcinoma.
BACKGROUND
The mitogenic kinin peptides formed by the serine protease, tissue kallikrein (TK1), stimulate the proliferation of tumour cells and, by increasing vascular permeability, enhance metastasis. Oesophageal mucosal epithelial cells are derived from the epithelial cell germ layer, which expresses the kallikrein-kinin cascade.


OBJECTIVE
To determine the cellular distribution of active TK1, prokallikrein, and the kinin B(1) and B(2) receptors in oesophageal carcinoma by immunocytochemistry and in situ hybridisation (ISH).


METHODS
Fifty oesophageal specimens (33 biopsies and 17 resections) and 10 control specimens adjacent to tumour or normal oesophageal biopsies were studied. Specific antibodies were used to determine the cellular localisation of TK1, prokallikrein, and the kinin B(1) and B(2) receptors in normal and oesophageal specimens by standard immunohistochemical techniques. The intensity of immunolabelling was quantified by image analysis. Antisense probes for TK1 and the kinin B(1) and B(2) receptors were also used to localise mRNA.


RESULTS
TK1 (active and prokallikrein) was expressed in the mucosa of normal and tumour oesophageal epithelium. In general, expression was highest in activated mast cells, followed by giant tumour cells. Immunolabelling results were confirmed by ISH experiments.


CONCLUSIONS
This is the first demonstration that TK1 and kinin B(1) and B(2) receptors are expressed in oesophageal carcinoma. Because TK1 released from tumour cells enzymatically generates mitogenic kinins from its endogenous substrate, kininogen, it is possible that third generation kinin receptor antagonists, which have been shown to be cytotoxic to cancer cells, may be useful therapeutic agents in this disease.
Dlamini
Z
Z
School of Anatomical Sciences, University of the Witwatersrand, Faculty of Health Sciences, 7 York Road, Parktown, Johannesburg 2193, South Africa. dlaminiz@anatomy.wits.ac.za
Bhoola
K D
KD
D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology; D015726:Giant Cells / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D016234:Kallikrein-Kinin System; D008407:Mast Cells / Q000378:metabolism; D043783:Receptor, Bradykinin B1 / Q000378:metabolism*; D043782:Receptor, Bradykinin B2 / Q000378:metabolism*; D020840:Tissue Kallikreins / Q000378:metabolism*; D015854:Up-Regulation
D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D020840:Tissue Kallikreins