Abstract
The mucin MUC5B has a critical protective function in the normal lung, salivary glands, esophagus, and gallbladder, and has been reported to be aberrantly expressed in breast cancer, the second leading cause of cancer-related deaths among women worldwide. To understand better the implication of MUC5B in cancer pathogenesis, the luminal human breast cancer cell line MCF7 was transfected with a vector encoding a recombinant mini-mucin MUC5B and was then infected with a virus to deliver a short hairpin RNA to knock down the mini-mucin. The proliferative and invasive properties in Matrigel of MCF7 subclones and subpopulations were evaluated in vitro. A xenograft model was established by subcutaneous inoculation of MCF7 clones and subpopulations in SCID mice. Tumor growth was measured, and the tumors and metastases were assessed by histological and immunological analysis. The mini-mucin MUC5B promoted MCF7 cell proliferation and invasion in vitro. The xenograft experiments demonstrated that the mini-mucin promoted tumor growth and MCF7 cell dissemination. In conclusion, MUC5B expression is associated with aggressive behavior of MCF7 breast cancer cells. This study suggests that MUC5B may represent a good target for slowing tumor growth and metastasis.
Highlights
Mucins are high molecular weight O-glycosylated proteins present at the surface of most epithelial cells
Expression of the endogenous MUC5B was studied by qRTPCR (TaqMan) and showed that the Ires-Luc clone and the Mini5B-Luc clone harbored a similar expression of MUC5B mRNA in comparison to the parental MCF7 cell line (Fig. 1C)
Immunohistochemistry showed that Mini5B was expressed and secreted at the cell surface of the Mini5B–Luc clone chosen whereas no staining with the anti-MUC5B antibody was observed in the Ires–Luc clone and in the MCF7 parental cell line (Fig. 1D)
Summary
Mucins are high molecular weight O-glycosylated proteins present at the surface of most epithelial cells. Secreted mucins comprise amino- and carboxy-terminal regions that share similar domains with the pro-von Willebrand factor. These mucins polymerize through these regions to form long polymers, which are secreted into the lumen of many organs. The central part of mucins contains large regions enriched in hydroxyamino acids and proline (Ser/Thr/Pro regions) that are substituted extensively with O-glycans. These Ser/Thr/Pro sequences differ in size and in sequence between mucins, are not conserved between species, and are usually organized in tandem repeats (TR). These tandemly repeated sequences are linked to or interrupted by a naked and hydrophobic domain rich in cysteine residues and called a CYS domain [4]
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