Protein profile of basal prostate epithelial progenitor cells—stage‐specific embryonal antigen 4 expressing cells have enhanced regenerative potential <i>in vivo</i>

Höfner, Thomas; Klein, Corinna; Eisen, Christian; Rigo‐Watermeier, Teresa; Haferkamp, Axel; Sprick, Martin R.

doi:10.1111/jcmm.12785

Cited by 5 publications

(4 citation statements)

References 29 publications

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“…Several investigators have shown that SSEA-4 plays an important role in malignant characteristics of PC, such as regenerative potential and the loss of epithelial phenotype [10, 21, 22]. However, no study has reported on the relationships between SSEA-4 expression in cancer cells and the clinicopathological features of PC patients.…”

Section: Discussionmentioning

confidence: 99%

Stage-specific embryonic antigen-4 is a histological marker reflecting the malignant behavior of prostate cancer

et al. 2019

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Stage-specific embryonic antigen-4 (SSEA-4), a specific marker for pluripotent stem cells, plays an important role in the malignant behavior of several cancers. Here, SSEA-4 expression was evaluated by immunohistochemistry using monoclonal antibody RM1 specific to SSEA-4 in 181 and 117 prostate cancer (PC) specimens obtained by biopsy and radical prostatectomy (RP), respectively. The relationships between SSEA-4 expression in cancer cells or the presence of SSEA-4-positive tumor-infiltrating immune cells (TICs) and clinicopathological parameters were analyzed. SSEA-4 expression in cancer cells was significantly associated with Gleason score, local progression, and lymph node and distant metastasis. In RP specimens, high SSEA-4 expression in cancer cells and the presence of SSEA-4-positive TICs were significant predictors of pT3, i.e., invasion and worse biochemical recurrence (BCR) after RP, respectively, in univariate analysis. In contrast, combination of high SSEA-4 expression in cancer cells and the presence of SSEA-4-positive TICs was an independent predictor for pT3 and BCR in multivariate analysis. Biologically this combination was also independently associated with suppression of apoptosis. Thus, the co-expression of SSEA-4 in cancer cells and TICs may have crucial roles in the malignant aggressiveness and prognosis of PC. Invasive potential and suppression of apoptosis may be linked to SSEA-4 expression.

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Section: Discussionmentioning

confidence: 99%

Stage-specific embryonic antigen-4 is a histological marker reflecting the malignant behavior of prostate cancer

et al. 2019

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“…Furthermore, SSEA-4 is a wellknown specific marker for pluripotent stem cells and a useful marker for identifying CSCs (17). Moreover, SSEA-4 expression is associated with remodeling and renewal in a variety of malignant cells (18)(19)(20) and is reportedly correlated with regenerative potential and loss of the epithelial phenotype in PC cells (21,22). Therefore, we hypothesized that SSEA-4 may be a CSC marker in PC, and that its expression might be associated with hormonal therapy resistance in these patients.…”

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confidence: 99%

Relationship Between Stage-specific Embryonic Antigen-4 and Anti-cancer Effects of Neoadjuvant Hormonal Therapy in Prostate Cancer

et al. 2020

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Background/Aim: Stage-specific embryonic antigen-4 (SSEA-4) expression is associated with malignant aggressiveness and is useful as a marker for identifying cancer stem cells. Our aim was to assess the relationship between hormonal therapy and SSEA-4 expression in prostate cancer (PC). Materials and Methods: SSEA-4 expression in paired specimens from PC patients who underwent neoadjuvant hormonal therapy (NHT) and radical prostatectomy (60 pre-NHT specimens and 60 post-NHT specimens) was evaluated using immunohistochemistry. Proliferation index (PI) and apoptotic index (AI) were also evaluated. Results: Post-NHT tissues had significantly elevated SSEA-4 expression whereas anti-tumor effects of NHT were inversely correlated with SSEA-4 expression level. SSEA-4 expression in post-NHT tissues was significantly associated with biochemical recurrence-free survival. SSEA-4 expression in the post-NHT tissues was positively associated with PI and negatively done with AI. Conclusion: SSEA-4 is a potential therapeutic target for limiting the malignant potential in hormone-naïve PC when considering the use of NHT.Prostate cancer (PC) is the most commonly diagnosed cancer among men and the second leading cause of cancer-related deaths among men in the United States (1). Although many patients with early PC have elevated serum concentrations of prostate-specific antigen (PSA), approximately one-third of patients already have metastasis at the time of diagnosis (2). In general, hormonal therapy involves androgendeprivation therapy (ADT), which is a standard and effective treatment for patients with metastatic PC. Unfortunately, the majority of androgen-dependent PC cells gradually become androgen-independent cells during ADT, which leads to metastatic PC becoming resistant to hormonal therapy and progressing to castration-resistant prostate cancer (CRPC) (3). There are various treatments for CRPC, which involve chemotherapeutic agents, androgen receptor-axis-targeted agents, and immunotherapeutic agents (4-6). While these treatments can improve survival outcomes in CRPC cases, the increase in progression-free survival (PFS) and overall survival (OS) remains suboptimal.The suboptimal outcomes in CRPC cases are partly related to our poor understanding of the molecular mechanisms that lead to hormonal therapy resistance. In this context, it is important to understand that cancer stem cells (CSCs) play important roles in PC tumor growth and treatment resistance, as their pluripotency and self-renewal capability allow these cells to differentiate into diverse new cancer cells (7). Sex determining region Y-box-2 (Sox-2) is a major CSC marker, and its expression in PC cells is increased after androgen deprivation. The latter has been positively associated with cell growth and resistance to anti-androgen agents in both androgen-dependent and androgen-independent PC cells (8). Therefore, it is important to understand the interactions between hormonal therapy and CSCs, which may provide insight regarding PC tumor development and resista...

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“…SSEA-4 (also known as sialyl-Gb5) plays an important role in prostate cancer development by affecting adhesion of cells to extracellular matrix ( Sivasubramaniyan et al, 2015 ) and facilitating precise recognition of basal epithelial stem cell/progenitor cell lineages ( Hofner et al, 2016 ). Disialosyl globopentaosylceramide (DSGb5) is expressed in benign prostate tissue but not in prostate cancer.…”

Section: Prostate and Ovarian Cancermentioning

confidence: 99%

Biological Roles of Aberrantly Expressed Glycosphingolipids and Related Enzymes in Human Cancer Development and Progression

Zhuo

Guan

2018

Front. Physiol.

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Glycosphingolipids (GSLs), which consist of a hydrophobic ceramide backbone and a hydrophilic carbohydrate residue, are an important type of glycolipid expressed in surface membranes of all animal cells. GSLs play essential roles in maintenance of plasma membrane stability, in regulation of numerous cellular processes (including adhesion, proliferation, apoptosis, and recognition), and in modulation of signal transduction pathways. GSLs have traditionally been classified as ganglio-series, lacto-series, or globo-series on the basis of their diverse types of oligosaccharide chains. Structures and functions of specific GSLs are also determined by their oligosaccharide chains. Different cells and tissues show differential expression of GSLs, and changes in structures of GSL glycan moieties occur during development of numerous types of human cancer. Association of GSLs and/or related enzymes with initiation and progression of cancer has been documented in 100s of studies, and many such GSLs are useful markers or targets for cancer diagnosis or therapy. In this review, we summarize (i) recent studies on aberrant expression and distribution of GSLs in common human cancers (breast, lung, colorectal, melanoma, prostate, ovarian, leukemia, renal, bladder, gastric); (ii) biological functions of specific GSLs in these cancers.

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Protein profile of basal prostate epithelial progenitor cells—stage‐specific embryonal antigen 4 expressing cells have enhanced regenerative potential in vivo

Cited by 5 publications

References 29 publications

Stage-specific embryonic antigen-4 is a histological marker reflecting the malignant behavior of prostate cancer

Stage-specific embryonic antigen-4 is a histological marker reflecting the malignant behavior of prostate cancer

Relationship Between Stage-specific Embryonic Antigen-4 and Anti-cancer Effects of Neoadjuvant Hormonal Therapy in Prostate Cancer

Biological Roles of Aberrantly Expressed Glycosphingolipids and Related Enzymes in Human Cancer Development and Progression

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