Expression of human beta-defensin-2 in intratumoral vascular endothelium and in endothelial cells induced by transforming growth factor beta.
Human beta-defensin-2 (hBD-2) is a small cationic peptide originally identified from psoriatic skin lesions as an antimicrobial agent of the innate immune system. The expression of hBD-2 is believed to be induced exclusively in epithelial cells by microbial components and certain proinflammatory cytokines, such as interleukin-1 beta (IL-1 beta). In this study, we report, for the first time, that hBD-2 is expressed in vascular endothelial cells associated with oral squamous cell carcinoma (OSCC) and Kaposi's sarcoma lesions, but not in that of normal stroma. Expression of hBD-2 in vascular endothelial cells was further substantiated by in vitro experiments using cultured human umbilical vein endothelial cells (HUVECs). Transforming growth factor beta1 (TGF beta 1) and IL-1 beta, two well-known tumorigenic inflammatory mediators, induce hBD-2 transcript and peptide expression in HUVECs. However, TGF beta 1 does not stimulate hBD-2 expression in oral epithelial cells. In addition, proinflammatory cytokines and microbial reagents do not induce the expression of hBD-1 and hBD-3 in HUVECs. Since hBD-2 has been shown to modulate migration, proliferation, and tube formation of HUVECs in vitro and participate in immune cell trafficking, its expression in vascular endothelial cells located within malignant lesions may play a role in tumor angiogenesis and cancer metastasis.
Kawsar
Hameem I
HI
Department of Biological Sciences, Case Western Reserve University School of Dental Medicine, 10900 Euclid Ave., Cleveland, OH 44106, USA.
Ghosh
Santosh K
SK
Hirsch
Stanley A
SA
Koon
Henry B
HB
Weinberg
Aaron
A
Jin
Ge
G
D002294:Carcinoma, Squamous Cell / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D009062:Mouth Neoplasms / Q000378:metabolism; D009369:Neoplasms / Q000098:blood supply / Q000378:metabolism*; D012514:Sarcoma, Kaposi / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D023083:beta-Defensins / Q000235:genetics / Q000378:metabolism*
C422950:DEFB103A protein, human; C106641:DEFB4A protein, human; D053583:Interleukin-1beta; D016212:Transforming Growth Factor beta; D023083:beta-Defensins