Bone marrow stromal cell antigen 2 is broadly expressed in the different pluripotent states of human pluripotent stem cells and regulates the expression of pluripotency genes and three germ layer markers.

Human pluripotent stem cells (hPSCs) have at least three distinct states: naïve pluripotency that represents the cellular states of the pre-implantation epiblast cells, primed pluripotency that represents the cellular states of the post-implantation epiblast cells, and formative pluripotency that represents a developmental continuum between naïve and primed pluripotency. Various cell surface markers have been used to define and analyze primed and naïve hPSCs within heterogeneous populations. However, not much is known about common cell surface markers for the different pluripotent states of hPSCs.

A monoclonal antibody recognizing CD98 on human embryonic stem cells shows anti-tumor activity in hepatocellular carcinoma xenografts.

CD98, also known as SLC3A2, is a multifunctional cell surface molecule consisting of amino acid transporters. CD98 is ubiquitously expressed in many types of tissues, but expressed at higher levels in cancerous tissues than in normal tissues. CD98 is also upregulated in most hepatocellular carcinoma (HCC) patients; however, the function of CD98 in HCC cells has been little studied.

Role of heat shock protein 60 in primed and naïve states of human pluripotent stem cells.

Human pluripotent stem cells (hPSCs) exist in at least two distinct states in mammals: naïve pluripotency that represents several molecular characteristics in pre-implantation epiblast and primed pluripotency that corresponds to cells poised for differentiation in post-implantation epiblast. To identify and characterize the surface molecules that are necessary for the maintenance of naïve hPSCs, we generated a panel of murine monoclonal antibodies (MAbs) specific to the naïve state of hPSCs. Flow cytometry showed that N1-A4, one of the MAbs, bound to naïve hPSCs but not to primed hPSCs.

Heterogeneous nuclear ribonucleoprotein A2/B1 regulates the ERK and p53/HDM2 signaling pathways to promote the survival, proliferation and migration of non‑small cell lung cancer cells.

Lung cancer is the most frequent cause of cancer‑associated mortality worldwide. Upregulation of heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2/B1) has been reported in non‑small cell lung cancer (NSCLC) cells, but its contribution to NSCLC remains poorly understood. hnRNPA2/B1 is involved in carcinogenesis by interacting with a number of proteins; however, little is known about its interaction with p53.

ETV2/ER71 regulates the generation of FLK1 cells from mouse embryonic stem cells through miR-126-MAPK signaling.

Previous studies including ours have demonstrated a critical function of the transcription factor ETV2 (ets variant 2; also known as ER71) in determining the fate of cardiovascular lineage development. However, the underlying mechanisms of ETV2 function remain largely unknown. In this study, we demonstrated the novel function of the miR (micro RNA)-126-MAPK (mitogen-activated protein kinase) pathway in ETV2-mediated FLK1 (fetal liver kinase 1; also known as VEGFR2) cell generation from the mouse embryonic stem cells (mESCs).

Mycoplasma infection promotes tumor progression via interaction of the mycoplasmal protein p37 and epithelial cell adhesion molecule in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is currently the third leading cause of cancer death worldwide. To study how mycoplasma infection affects HCC progression, we investigated the characteristics of mycoplasma-infected tumor tissues and circulating tumor cells (CTCs) in HCC patients. The mycoplasmal membrane protein p37 showed significant correlations with higher histologic stages and vascular invasion and predicted poor disease-free survival of HCC patients.

Epitope mapping of anti-PGRMC1 antibodies reveals the non-conventional membrane topology of PGRMC1 on the cell surface.

Progesterone receptor membrane component1 (PGRMC1) is a heme-binding protein involved in cancers and Alzheimer's disease. PGRMC1 consists of a short N-terminal extracellular or luminal domain, a single membrane-spanning domain, and a long cytoplasmic domain. Previously, we generated two monoclonal antibodies (MAbs) 108-B6 and 4A68 that recognize cell surface-expressed PGRMC1 (csPGRMC1) on human pluripotent stem cells and some cancer cells.

Progesterone Receptor Membrane Component 1 suppresses the p53 and Wnt/β-catenin pathways to promote human pluripotent stem cell self-renewal.

Progesterone receptor membrane component 1 (PGRMC1) is a multifunctional heme-binding protein involved in various diseases, including cancers and Alzheimer's disease. Previously, we generated two monoclonal antibodies (MAbs) 108-B6 and 4A68 against surface molecules on human pluripotent stem cells (hPSCs). Here we show that PGRMC1 is the target antigen of both MAbs, and is predominantly expressed on hPSCs and some cancer cells.

Enhanced expression of cell-surface B-cell receptor-associated protein 31 contributes to poor survival of non-small cell lung carcinoma cells.

B-cell receptor-associated protein 31 (BAP31) is an endoplasmic reticulum (ER) membrane protein which plays a role as a molecular chaperone for the newly synthesized transmembrane proteins. BAP31 is also an important apoptosis regulator for extrinsic apoptosis induction in the ER membrane. Recent studies have shown that BAP31 is also expressed on the surface of embryonic stem cells.

Cell-surface major vault protein promotes cancer progression through harboring mesenchymal and intermediate circulating tumor cells in hepatocellular carcinomas.

Circulating tumor cells (CTCs) play a major role in the metastasis and recurrence of hepatocellular carcinoma (HCC). Here, we found that major vault protein (MVP) is expressed on the surface of HCC cells and further induced under stressful environments. MVP knockdown reduces cell proliferation and induces apoptosis in HCC cells.

Correction: Mapping of a Mycoplasma-Neutralizing Epitope on the Mycoplasmal p37 Protein.

[This corrects the article DOI: 10.1371/journal.pone.

Correction: Epitope Mapping of Antibodies Suggests the Novel Membrane Topology of B-Cell Receptor Associated Protein 31 on the Cell Surface of Embryonic Stem Cells: The Novel Membrane Topology of BAP31.

[This corrects the article DOI: 10.1371/journal.pone.

Mapping of a Mycoplasma-Neutralizing Epitope on the Mycoplasmal p37 Protein.

Many studies have shown that the mycoplasmal membrane protein p37 enhances cancer cell migration, invasion, and metastasis. Previously, we generated 6 monoclonal antibodies (MAbs) against the mycoplasmal protein p37 and showed the presence of mycoplasma-infected circulating tumor cells in the blood of hepatocellular carcinoma patients by using CA27, one of the six MAbs. When mycoplasmas were incubated with cancer cells in the presence of CA27, mycoplasma infection was completely inhibited, suggesting that CA27 is a neutralizing antibody inhibiting mycoplasma infection.

In vivo Evaluation of Human Embryonic Stem Cells Isolated by 57-C11 Monoclonal Antibody.

Background: The normal cells derived from human embryonic stem cells (hESCs) are regarded as substitutes for damaged or dysfunctional adult cells. However, tumorigenicity of hESCs remains a major challenge in clinical application of hESC-derived cell transplantation. Previously, we generated monoclonal antibody (MAb) 57-C11 specific to the surface molecule on undifferentiated hESCs.

Injury-Mediated Vascular Regeneration Requires Endothelial ER71/ETV2.

Objective: Comprehensive understanding of the mechanisms regulating angiogenesis might provide new strategies for angiogenic therapies for treating diverse physiological and pathological ischemic conditions. The E-twenty six (ETS) factor Ets variant 2 (ETV2; aka Ets-related protein 71) is essential for the formation of hematopoietic and vascular systems. Despite its indispensable function in vessel development, ETV2 role in adult angiogenesis has not yet been addressed.

Epitope Mapping of Antibodies Suggests the Novel Membrane Topology of B-Cell Receptor Associated Protein 31 on the Cell Surface of Embryonic Stem Cells: The Novel Membrane Topology of BAP31.

When located in the endoplasmic reticulum (ER) membrane, B-cell receptor associated protein 31 (BAP31) is involved in the export of secreted proteins from the ER to the plasma membrane. In a previous study, we generated two monoclonal antibodies (mAbs), 297-D4 and 144-A8, that bound to surface molecules on human embryonic stem cells (hESCs), but not to surface molecules on mouse embryonic stem cells (mESCs). Subsequent studies revealed that the mAbs recognized BAP31 on the surface of hESCs.

B-cell receptor-associated protein 31 regulates human embryonic stem cell adhesion, stemness, and survival via control of epithelial cell adhesion molecule.

B-Cell receptor-associated protein 31 (BAP31) regulates the export of secreted membrane proteins from the endoplasmic reticulum (ER) to the downstream secretory pathway. Previously, we generated a monoclonal antibody 297-D4 against the surface molecule on undifferentiated human embryonic stem cells (hESCs). Here, we found that 297-D4 antigen was localized to pluripotent hESCs and downregulated during early differentiation of hESCs and identified that the antigen target of 297-D4 was BAP31 on the hESC-surface.

Detection of mycoplasma infection in circulating tumor cells in patients with hepatocellular carcinoma.

Many studies have shown that persistent infections of bacteria promote carcinogenesis and metastasis. Infectious agents and their products can modulate cancer progression through the induction of host inflammatory and immune responses. The presence of circulating tumor cells (CTCs) is considered as an important indicator in the metastatic cascade.

Antibody approaches to prepare clinically transplantable cells from human embryonic stem cells: identification of human embryonic stem cell surface markers by monoclonal antibodies.

Human embryonic stem cells (hESCs) are unique cell populations, possessing both unlimited self-renewal capacity and pluripotency, i.e. the potential to give rise to all kinds of specialized cells in the human body.

Characterization of monoclonal antibodies recognizing 130 kDa surface proteins on human embryonic stem cells and cancer cell lines.

To study cell surface proteins expressed on human embryonic stem cells (hESCs), we generated a panel of monoclonal antibodies (MAbs) against undifferentiated hESCs by a decoy immunization strategy in a previous study. Two of the MAbs, 63-B6 and 246-D7, bound to human pluripotent stem cells but not to human primary cells such as human peripheral blood mononuclear cells and human lung fibroblasts. They did not bind to either mouse embryonic stem cells or mouse embryonic fibroblasts.

Heterogeneous nuclear ribonucleoprotein A2/B1 regulates the self-renewal and pluripotency of human embryonic stem cells via the control of the G1/S transition.

Self-renewal and pluripotency of human embryonic stem cells (hESCs) are a complex biological process for maintaining hESC stemness. However, the molecular mechanisms underlying these special properties of hESCs are not fully understood. Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1) is a multifunctional RNA-binding protein whose expression is related to cell proliferation and carcinogenesis.

Effects of the pro-inflammatory milieu on the dedifferentiation of cultured fibroblast-like synoviocytes.

The aim of this study was to determine whether the inflammatory milieu and/or hypoxia induces the dedifferentiation of synovial cells into mesenchymal stem-like cells, which may contribute to the tumor-like growth of synovial cells. Expression of mesenchymal stem cell markers (CD24, CD44, CD90, CD106, CD146 and Stro-1) was compared among cultured fibroblast-like synoviocytes (FLSs) from patients with rheumatoid arthritis (RA) or osteoarthritis (OA), bone marrow mesenchymal stem cells (BM MSCs) and normal dermal fibroblasts. After the cells were stimulated with pro-inflammatory cytokines for 3 days under hypoxia or normoxia, the stem cell markers were analyzed by FACS.

Detection and characterization of 2-E2-specific surface protein in human pluripotent stem cells.

To investigate cell surface antigens on human embryonic stem cells (hESCs), we generated a panel of monoclonal antibodies (MAbs) against undifferentiated hESCs by a decoy immunization strategy. One of the MAbs, MAb 2-E2, specifically bound to human pluripotent stem cells but not to mouse pluripotent stem cells and mouse embryonic fibroblasts. 2-E2 also bound to human differentiated cells, peripheral blood monocytes, and dermal fibroblasts.

Identification and characterization of adenovirus early region 1B-associated protein 5 as a surface marker on undifferentiated human embryonic stem cells.

Pluripotent human embryonic stem cells (hESCs) provide appropriate systems for developmental studies and prospective donor cell sources for regenerative medicine. Identification of surface markers specific to hESCs is a prerequisite for studying hESC biology and can be used to generate clinical-level donor cell preparations that are free from tumorigenic undifferentiated hESCs. We previously reported the generation of monoclonal antibodies that specifically recognize hESC surface antigens using a decoy immunization strategy.

L1 cell adhesion molecule is a novel therapeutic target in intrahepatic cholangiocarcinoma.

Purpose: Intrahepatic cholangiocarcinoma (ICC), a highly malignant hepatobiliary cancer, has a poor prognosis and is refractory to conventional therapies. The aim of this study is to discover a novel molecular target for the treatment of ICC.

Experimental Design: To discover novel cancer-associated membrane antigens expressed in ICC cells, we generated monoclonal antibodies (mAb) by immunizing mice with intact ICC cell lines and screened for those that bind to the plasma membrane of ICC cells but not to normal cells.