Monoclonal antibodies to early pregnancy factor perturb tumour cell growth

Abstract

SUMMARYThe pregnancy-associated substance early pregnancy factor (EPF) has previously been reported as a product of tumours of germ cell origin. More recently EPF (or an EPF-related substance, tEPF) has aiso been detected in the serum of patients bearing tumours of non-germ cell origin. We report here the production oftEPF by a variety of cultured transformed and tumour eell lines, of both germ and non-germ celt origin. Antibodies specific for EPF remove all tEPF activity from tumottr cell conditioned medium. tEPF production is found to be associated with cell division; tEPF is no longer detected after growth arrest or differentiation. Co-eulUire of tumour eells with increasing doses of anti-EPF monoclonal antibodies resulted in a significant, dose-dependent decrease in rate of cell growth and viability. Similar anti-EPF concentrations had no effect on the concanavalin A induced proliferation of mouse spleen cells. These studies suggest, therefore, that tEPF is a growth-regulated product of cultured tumour and transformed ceils. These celts are also dependent upon tEPF for continued growth, i.e. tEPF is acting in the autocrine mode.

Human Hsp10 and Early Pregnancy Factor (EPF) and their relationship and involvement in cancer and immunity: Current knowledge and perspectives

“…These findings suggest that EPF (and/or similar substances) is produced by cells that need extra support for high level protein synthesis and/or proliferation, thus being implicated not only in pregnancy-related events, but also in cancer progression. In support of this concept, it has been demonstrated, using in vitro models, that monoclonal antibodies to EPF perturb tumor cell growth (Quinn et al 1990). As discussed earlier in this article, possible implications of Hsp10 in cancer progression can be envisioned, considering the observed Hsp10 increase in the cytosol during the carcinogenetic steps that occur in tumors of the exocervix (Cappello et al 2003a), prostate (Cappello et al 2003b) and large bowel (Cappello et al 2005).…”

Identification of Candidate Biomarker Proteins Released by Human Endometrial and Cervical Cancer Cells Using Two-Dimensional Liquid Chromatography/Tandem Mass Spectrometry

“…40,41 Our analyses show that extracellular chaperonin 10 carries two post-translational modifications at the N-terminus. 35,42 Extracellular chaperonin 10 probably functions as an immunosuppressant 41 and a growth factor 43 in neoplastic cell proliferation. PK-M2 is expressed selectively in metastatic cells, [44][45][46][47] primarily in its dimeric form.…”

Identification of heat shock protein 10 within the equine embryo, endometrium, and maternal peripheral blood mononuclear cells

“…This has spawned a variety of studies in cancer research concentrating on advanced serous papillary ovarian carcinoma [31] and HSP10 expression in large bowel carcinomas [32] as well as Crohn disease and ulcerative colitis [33]. The stimulus for this research follows prior demonstration that administration of anti-EPF monoclonal antibodies slowed tumor development when provided at the same time as tumor cell inoculation because of the decrease in tumor cell DNA synthesis [30]. Interestingly, Hsp10 has specifically been isolated within both pathologic and normal endometrial samples from women in a study intended to identify and validate biomarkers capable of discriminating malignant and pathologic endometrium from benign [34], and the extracellular form has been affiliated with secretion in both endometrial and ovarian cancers [19].…”

“…Additional research on Hsp10 has focused on whether the same genes that allow cancer cells to divide rapidly and migrate to new tissue sites are the same genes that control differentiation of the conceptus [30]. This has spawned a variety of studies in cancer research concentrating on advanced serous papillary ovarian carcinoma [31] and HSP10 expression in large bowel carcinomas [32] as well as Crohn disease and ulcerative colitis [33].…”