Inhibition of EGFR pathway signaling and the metastatic potential of breast cancer cells by PA-MSHA mediated by type 1 fimbriae via a mannose-dependent manner.

Abstract

To identify more therapeutic targets and clarify the detailed mechanisms of Pseudomonas aeruginosa-mannose-sensitive hemagglutinin (PA-MSHA) on breast cancer cells both in vitro and in vivo. PA-MSHA was administered to epidermal growth factor receptor (EGFR)-positive human breast cancer cell lines MDA-MB-231HM and MDA-MB-468 in vitro and to mice bearing tumor xenografts. The mannose cocultured test was used to detect the effect of mannose on PA-MSHA-induced cell proliferation, cell cycle arrest, apoptosis, and EGFR pathway signaling. We found that cells stimulated with PA-MSHA exhibited a downregulation of EGFR signaling. The addition of mannose partially inhibited the PA-MSHA-stimulated cell anti-proliferative effect, cell apoptosis, cell cycle arrest, activation of apoptosis-associated caspases, and even downregulation of the EGFR signaling pathway. In vivo, PA-MSHA treatment significantly suppressed mammary tumorigenesis in xenografts in mice and decreased lung metastasis in MDA-MB-231HM cell-transplanted mice. Tumor sample analyses confirmed inhibition of the EGFR pathway in the PA-MSHA-treated mice. In conclusion, this study showed that the involvement of the mannose-mediated EGFR pathway has a critical function in the preclinical rationale for the development of PA-MSHA for the treatment of human breast cancer. It also suggests the potentially beneficial use of PA-MSHA in adjuvant therapy for breast tumors with EGFR overexpression.

• Authors: Z-B Liu, Y-F Hou, J Zhu, D-L Hu, W Jin, Z-L Ou, G-H Di, J Wu, Z-Z Shen, Z-M Shao
• Journal: Oncogene (Oncogene) Vol. 29 Issue 20 Pg. 2996-3009 (May 20 2010) ISSN: 1476-5594 [Electronic] England
• PMID: 20228837 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Hemagglutinins
• RNA, Messenger
• RNA, Small Interfering
• EGFR protein, human
• ErbB Receptors
• Mannose

Topics

• Animals
• Apoptosis (drug effects)
• Blotting, Western
• Breast Neoplasms (metabolism, pathology, prevention & control)
• Cell Adhesion (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Enzyme-Linked Immunosorbent Assay
• ErbB Receptors (antagonists & inhibitors, genetics, metabolism)
• Female
• Fimbriae, Bacterial (metabolism)
• Flow Cytometry
• Hemagglutinins (pharmacology)
• Humans
• Lung Neoplasms (metabolism, prevention & control, secondary)
• Mannose (metabolism)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasm Transplantation
• Pseudomonas aeruginosa (metabolism)
• RNA, Messenger (genetics, metabolism)
• RNA, Small Interfering (pharmacology)
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction