Effects of CD40 binding on ovarian carcinoma cell growth and cytokine productionin vitro

Abstract

SummaryThe poor prognosis associated with ovarian carcinoma (OVCA) is linked to the high incidence of local recurrence. There is a pressing need to identify factors that can play a role in OVCA growth and spread. Here, we focused on CD40, a member of the tumour necrosis factor (TNF) receptor superfamily with important functions in immune response. The expression of CD40 has been reported on various types of carcinoma cells, but its biological role is still poorly understood. The aim of the present study was to investigate the expression and function of the CD40 in OVCA cell lines. Detectable CD40 levels ranging from low to very high were found on the cell surface of several OVCA cell lines by flow cytometry analysis. Co-culture with a murine cell line transfected with CD40 ligand (CD40L) inhibited cell growth and up-regulated the secretion of proinflammatory cytokines interleukin (IL)-6, IL-8 and TNF-a in high-level CD40-expressing OVCA cell lines. Similarly, an increase of IL-6 and IL-8 release could be obtained by adding a soluble form of CD40L to the OVCA cultures. These results suggest that CD40-CD40L interaction is an important pathway affecting growth regulation and cytokine production in OVCA.

CD40 Expression in Human Esophageal Squamous Cell Carcinoma Is Associated with Tumor Progression and Lymph Node Metastasis

“…This result is in contrast to previous reports of a direct anti-proliferative effect induced by CD40-CD154 interaction in various cancer cells in vitro or in vivo (30,31). On the other hand, recent studies demonstrated that stimulation of CD40 protects human bladder carcinoma cells from apoptosis (32), and that a low level of CD40 expression on tumor cells was not associated with cell growth in head and neck squamous cell cancer and ovarian cancer (27,33). Thus, the effect of CD40 on tumor proliferation differs depending on the cancer type, and in ESCC, a direct anti-proliferative effect of CD40 may not be evident due to the low level of CD40 expression in the ESCC cell lines (less than 20%).…”

“…In the present study, a significant increase in IL6 production was induced by rhCD154 in ESCC cell lines, even in the cell line with low CD40 expression. Previous studies have demonstrated that CD40 induces the up-regulation of IL6 production in various tumors including multiple myeloma (36), breast cancer (35), ovarian carcinoma (33), and non-small cell lung cancer (37). Furthermore, IL6 has been reported to induce tumor progression in various human malignancies, including esophageal cancer (38).…”

Imbalance in serum soluble CD30/CD30L and CD40/CD40L systems are associated with ovarian tumors

“…CD40-CD40L system is strongly controlled by cytokine and growth factors cross talk in ovarian tumors cross-talk. Toutirais et al [25] found y detectable CD40 levels ranging from low to very high on the cell surface of several ovarian cancer OVCA cell lines Co-culture with the murine fibroblasts, showing CD40L expression effected in the inhibited cell growth and up regulated secretion of the proinflammatory cytokines. Similar results were obtained following treatment with sCD40L.…”

Cationic liposome-mediated transfection of CD40 ligand gene inhibits hepatic tumor growth of hepatocellular carcinoma in mice

“…Treatment not only appears capable of inducing a cellular anti-leukemia immunity, but also may have a direct effect on leukemia cells by inducing latent sensitivity to Fas (CD95)-dependent leukemia cell apoptosis (Saudemont et al, 2002). Recently, many investigators have reported that ex vivo transduction of tumor cells with the mCD40L gene or in vivo transfection of the mCD40L gene was able to induce antitumor immunity against different tumor cell lines in subcutaneous tumor models, such as colorectal cancer (Georgopoulos et al, 2007), lung cancer (Noguchi et al, 2001;Tada et al, 2003), colon cancer (Sun et al, 2000;Buning et al, 2002), urologic malignancies (Loskog et al, 2001;Hussain et al, 2003), melanoma (Peter et al, 2002), ovarian carcinoma (Toutirais et al, 2007) and malignant mesothilima (Friedlander et al, 2003). Schmitz et al(2001) used adenovirus-mediated CD40L gene therapy of orthotopic HCC, demonstrating that it abrogated HCC cells tumorigenicity when expressing mCD40L gene, and led to completely established tumor eradication and long-term survival in most of treated animals.…”

“…The endogenous production of IL-12 resulting from the CD40L-CD40 interaction may play a role in the persistence of the antitumor effects (Harada et al, 1998;Toutirais et al, 2007). CD40 activation through CD40L-CD40 interaction may become a potential tool in malignant neoplasms (Ottaiano et al, 2002;Bereznaya and Chekhun, 2007).…”