The role of free beta subunit of human chorionic gonadotropin in high-grade serous cancer

The beta-subunit of human chorionic gonadotropin (hCG-β) is elevated in a range of cancers, including high-grade serous cancer (HGSC), and has been associated with poor response to radiotherapy and chemotherapy. Women with HGSC frequently respond to first-line treatment with the platinum-based chemotherapeutic drug carboplatin, but relapse due to chemoresistance. This study aimed to characterise expression of hCG-β in HGSC cell lines and to determine whether hCG-β has a role in the responsiveness of these cells to platinum-drugs. qRT-PCR and ELISA were used to determine endogenous levels of hCG-β in seven HGSC cell lines. hCG-β was down-regulated in HEY and A2780cis (cisplatin resistant) cells and their sensitivity to cisplatin determined. The proteomic technique iTRAQ was used to determine the mechanism(s) by which hCGβ might be involved in cisplatin sensitivity. It was found that all cell lines expressed hCG-β at various levels. Further, downregulation of hCG-β in HEY and A2780cis cells increased their sensitivity to cisplatin, carboplatin and oxaliplatin. iTRAQ results showed differences in proteins associated with the cell cycle, cell death and survival, as well as DNA replication, damage and repair pathways. These findings suggest that hCG-β might have a role in modulating the sensitivity of some HGSCs to platinum-based chemotherapeutics

Cell attachment to peptide modified glass surfaces.

Cell attachment is vital for the integration of biomaterials in the body. Surface modification using cell adhesive peptides, such as Arginine-Glycine-Aspartic (RGD), has showed promise for enhancing cell adhesion. Cell adhesion on glass and polyethylene glycol (PEGylated) surfaces modified with active RGD and Proline-Histidine-Serine-Arginine-Asparagine (PHSRN) peptides as well as inactive RDG and HRPSN control peptides was investigated in serum free conditions using three cell lines; NIH3T3 fibroblasts, MC3T3 pre-osteoblasts and C2C12 pre-myoblasts.Peptide attachment to glass surfaces was confirmed by x-ray photoelectron spectroscopy and contact angle measurements. Cell attachment and spreading was equivalent on all peptide and fibronectin coated glass surfaces and was significantly higher than on unmodified glass after 3 hours. Cell attachment to the peptide modified glass wasreduced in the presence of soluble RGD and RDG peptides, indicating that cell attachment to these surfaces may be integrin mediated, but not specific for RGD.Inhibition of protein synthesis with cycloheximide revealed that endogenous protein synthesis did not influence the specificity of cell attachment to the peptide modified glass surfaces in all cell types within a 3 hour period. However, cycloheximide treatment inhibited cell spreading on the peptide modified glass surfaces, suggestingthat proteins synthesis was required for spreading. Long term adhesion studies, within a24 hour period, showed that all cell lines were able to remain attached to the peptide modified glass surfaces, while C2C12 and MC3T3 cells were also able to form focal adhesions during this period. Cell attachment to peptide modified PEGylated surfaces over a 3 hour period showed that NIH3T3 and C2C12 cells experienced significantly higher levels of cell attachment on the RGD modified surface compared to the otherpeptides. MC3T3 cells attached to all the peptide modified PEGylated surfaces to the same extent, suggesting that cell attachment to peptide modified PEGlyated surfaces, can be cell type dependent.In conclusion all the peptides were able to promote cell adhesion on glass surfaces in the absence of a PEG linker. In the presence of a PEG linker cellular response to the peptide surfaces was both peptide and cell type dependent