Surface keratin 1, a tumor-selective peptide target in human triple-negative breast cancer

Area of Science:

• Oncology
• Cell Biology
• Biochemistry

Background:

• Targeted drug delivery to cancer cells relies on identifying specific cell-surface receptors.
• Triple-negative breast cancer (TNBC) presents a challenge due to the lack of well-defined receptors for targeted therapies.
• Selective targeting requires receptors overexpressed in cancer cells but not in normal tissues.

Purpose of the Study:

• To identify a novel cell-surface receptor target for selective drug delivery in triple-negative breast cancer (TNBC).
• To investigate the expression levels and localization of keratin 1 (K1) in TNBC.
• To evaluate the potential of K1 as a target for peptide-mediated drug delivery.

Main Methods:

• Immunohistochemical (IHC) analysis of human TNBC and normal breast tissues.
• Mass spectrometry, peptide mass fingerprinting, and Western blot analysis of TNBC and normal cell lysates.
• Immunofluorescence confocal microscopy to detect cell-surface K1 expression.
• Assessment of peptide 18-4 uptake mediated by cell-surface K1.

Main Results:

• Human TNBC tissues exhibit significantly higher levels of keratin 1 (K1) compared to normal breast tissues.
• Grade 3 TNBC tumors show threefold higher K1 expression than grade 2 tumors.
• Cell-surface K1 is uniformly present on TNBC cells but absent or minimal on normal mammary epithelial cells.
• TNBC-selective peptide 18-4 utilizes cell-surface K1 for endocytosis, demonstrating K1-mediated targeted uptake.

Conclusions:

• Keratin 1 (K1) is significantly overexpressed in human triple-negative breast cancer (TNBC).
• Cell-surface K1 is a promising and selective target for directed drug delivery in TNBC.
• Peptide 18-4 demonstrates effective K1-mediated uptake in TNBC cells, validating K1 as a therapeutic target.