ITIH5-Derived Polypeptides Covering the VIT Domain Suppress the Growth of Human Cancer Cells In Vitro

Area of Science:

• Biochemistry
• Oncology
• Molecular Biology

Background:

• Targeting oncogenic drivers like mutated EGFR is common in cancer drug development.
• Restoring tumor suppressor protein function presents an alternative therapeutic strategy.
• Inter-alpha-trypsin inhibitor heavy chain 5 (ITIH5) is a known metastasis suppressor in breast and pancreatic cancers.

Purpose of the Study:

• To investigate the potential of ITIH5 in suppressing tumor growth beyond metastasis.
• To identify smaller ITIH5 fragments with retained growth inhibitory properties for drug development.
• To explore the role of the ITIH5-specific VIT domain in tumor suppression.

Main Methods:

• Overexpression of ITIH5 in MDA-MB-231 breast cancer cells.
• Transplantation of engineered cells into nude mice.
• Cloning and synthesis of truncated, His-tagged ITIH5 N-terminal polypeptides (ITIH5^681aa and ITIH5^161aa).
• In vitro testing of ITIH5 variants on various cancer cell lines (breast, bladder, lung).

Main Results:

• ITIH5 overexpression suppressed tumor growth by 85% in vivo.
• Recombinant ITIH5 polypeptides containing the VIT domain inhibited cancer cell proliferation dose-dependently (up to 50%).
• ITIH5 variants demonstrated efficacy across multiple cancer cell lines, including MDA-MB-231, SCaBER, and A549.

Conclusions:

• The VIT domain of ITIH5 is crucial for its tumor suppressor activity.
• Extracellular administration of ITIH5 peptides mimics full-length ITIH5 effects.
• ITIH5 peptides represent a promising basis for novel anticancer drug development.