MUC1 is a Promising Therapeutic Target for Prostate Cancer Therapy

Abstract

Prostate cancer (CaP) is one of the most common malignancies in men, and the incidence of CaP is increasing. Because of the limitations of current therapeutic approaches, many patients die of secondary disease (metastases). Mucins are used as diagnostic markers as well as therapeutic targets due to their aberrant and unique expression pattern during cancer progression. There is a growing interest in mucins as treatment targets in human malignancies, including CaP. So far, 21 mucin genes have been identified. Of these, MUC1 has been investigated most extensively. In neoplastic tissues, MUC1 is underglycosylated compared with that in normal tissues. The reduced glycosylation permits the immune system to access the peptide core of the tumor-associated underglycosylated MUC1 antigen (uMUC1) and reveal epitopes that are masked in the normal cell. This feature makes it possible to design an antibody that discriminates between normal and adenocarcinoma cells and target tumor-associated MUC1 with toxins or radionuclides, or use a vaccine targeting tumor-associated MUC1 antigen. The results from our recent study have shown that over-expression of MUC1 plays a very important role in CaP progression and MUC1 is an ideal target for targeted therapy to control micrometastases and hormone refractory disease. This review will cover our current understanding of the structure and functions of MUC1, summarize its expression on human CaP tissues and focus on the MUC1-based immunotherapy for control of metastatic CaP.

Evaluation of a Novel Anti-Mucin 1 (MUC1) Antibody (PankoMab) as a Potential Diagnostic Tool in Human Ductal Breast Cancer; Comparison with Two Established Antibodies

“…Only in one subgroup of lymph node-positive, ER-negative tumors, we found significantly reduced DF3 staining in G3 comparedtoG2tumors.VU-4-H5showedincreasedstaining intensityincorrelationwithincreasedgradingandlymphnode involvement, a result in contrast to the data of Luna-More [17],whichwereobtainedwithanotheranti-MUC1antibody (E29)andconsideredthecellulardistributionoftheantigen. BecauseVU-4-H5detectsMUC1withlessglycosylatedsugar chains and as glycosylation of mucins is often reduced with tumor progression [35][36][37], our results on VU-4-H5 staining areinconcordancewiththesefindings.…”

Prostate cancer genes associated with TMPRSS2–ERG gene fusion and prognostic of biochemical recurrence in multiple cohorts

“…Although translation of any such prognostic test would require more analysis and validation, not only by reverse transcriptase PCR but also in other independent cohorts, this study contributes to the current body of knowledge with respect to identifying biomarkers with the potential to improve prostate cancer patient management. Furthermore, certain genes that we found prognostic of recurrence, which were not validated in the Minnesota cohort, have previously been linked to prostate cancer progression, such as mucin 1 (Cozzi et al, 2005), which has also been proposed as a candidate for targeted therapy (Li and Cozzi, 2007), and may warrant further consideration as a prognostic biomarker. Figure 3A) is composed of mRNAs replicated as prognostic of recurrence in this experiment and a 596-patient Minnesota experiment (Nakagawa et al, 2008).…”

Characterisation of the new EpCAM-specific antibody HO-3: implications for trifunctional antibody immunotherapy of cancer

“…A potential impact of post-translational modification of EpCAM on the binding of therapeutic antibodies available so far remained entirely unexplored. Nevertheless, this may be of major importance as suggested by the tumour antigen MUC-1 whose hypoglycosylated variant expressed in tumour tissue is differentially recognised by mucin-specific antibodies (Grinstead et al, 2002;Karsten et al, 2005;Li and Cozzi, 2007). However, HO-3 binding to EpCAM was entirely independent of the presence of glycosyl residues on the target protein.…”