ABSTRACT
Human chorionic gonadotropin (hCG) was initially believed to be secreted exclusively by the embryo with its primary function being “rescue” of the corpus luteum. However, recently it has been found that the hormone (or its individual subunits) is also secreted by many cancers and that in many cases secretion is associated with poor patient prognosis. In this study, we assessed the presence of hCG in colorectal cancer cells (CCL-253) and evaluated the anti-tumour effects of anti-hCG antibodies in vitro and in vivo. Anti-hCG antibodies were reactive with CCL-253, as revealed by confocal immunoflourescence microscopy; both cell surface and intracellular expression were observed. Western blot analysis showed that antibodies appeared to interact with several moieties, indicating a level of cross-reactivity. Anti-hCG antiserum specifically reduced the viability of tumor cells and the addition of complement increased in vitro anti-tumor effects. In nude mice implanted with CCL-253 cells, administration of anti-hCG antiserum caused a significant reduction in tumor volume; all treated animals survived, while mortality was observed in control animals. Results suggest that anti-hCG antibodies can mediate significant anti-tumor activity both in vitro and in vivo and lend support to the rationale of anti-hCG immunization in the therapy of gonadotropin- sensitive cancers.
Subject(s)
Animals , Antigens, Neoplasm/immunology , Cell Line, Tumor , Cell Proliferation/drug effects , Chorionic Gonadotropin/antagonists & inhibitors , Chorionic Gonadotropin/immunology , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/immunology , Colorectal Neoplasms/pathology , Female , Humans , Immune Sera/immunology , Immune Sera/pharmacology , Mice , Time Factors , Xenograft Model Antitumor AssaysABSTRACT
A cDNA library of ovine pituitary DNA in plasmid pBR322 has been constructed by conventional methods with certain modifications. The library was screened using partial cDNAs for rat α-subunit and LHβ. We have isolated cDNA clones for ovine α- subunit and LHβ. The identification of these clones was confirmed by partial sequencing. The clones bear about 80% sequence homology with the respective rat cDNAs in the sequenced regions and hybridize with the rat clones in 5 X SSC at 55°C. The ovine LHβ clone has an insert of about 650 bp and selects an RNA of about 750 bases in a northern blot. The α-subunit cDNA clone has an insert of about 550 bp; it has two internal Pst I sites and thus shows restriction-based differences from rat α-subunit cDNA, which does not have any Pst I site.