Monoclonal antibodies against autocrine motility factor suppress gastric cancer

Area of Science:

• Oncology
• Molecular Biology
• Immunotherapy

Background:

• Autocrine motility factor (AMF), a secreted phosphoglucose isomerase, promotes cancer cell proliferation, survival, metastasis, and angiogenesis.
• AMF's role in tumor growth and its potential as a therapeutic target are under investigation.

Purpose of the Study:

• To investigate the efficacy of inhibiting AMF using targeted antibodies in suppressing cancer growth.
• To explore the potential of AMF-specific antibodies as a therapeutic strategy for cancer, particularly gastric cancer.

Main Methods:

• Utilized a Boyden chamber migration assay to measure AMF's effect on cancer cell motility.
• Administered recombinant human AMF (rhAMF) to various cancer cell lines and xenografted mice.
• Treated A549 xenografts with sunitinib or cetuximab and monitored plasma AMF levels and tumor weight.
• Tested a monoclonal antibody (9A-4H) against AMF in NCI-N87 gastric cancer xenografts.

Main Results:

• rhAMF increased motility in MDA-MB-231 and A549 cells but not in NCI-N87 or HepG2 cells.
• No clear correlation was observed between AMF receptor expression and rhAMF-stimulated cell motility.
• In A549 xenografts, decreased plasma AMF correlated with reduced tumor weight after sunitinib or cetuximab treatment.
• The 9A-4H antibody significantly suppressed NCI-N87 gastric tumor growth in mice.

Conclusions:

• AMF plays a significant role in promoting cancer cell motility and tumor growth.
• Antibodies targeting AMF demonstrate significant anticancer activity, particularly in gastric cancer models.
• AMF-specific antibodies represent a promising new therapeutic avenue for gastric cancer treatment.