Immunotherapeutic Targeting of NG2/CSPG4 in Solid Organ Cancers

Abstract

: Neuro-glia antigen 2/chondroitin sulfate proteoglycan 4 (NG2/CSPG4, also called MCSP, HMW-MAA, MSK16, MCSPG, MEL-CSPG, or gp240) is a large cell-surface antigen and an unusual cell membrane integral glycoprotein frequently expressed on undifferentiated precursor cells in multiple solid organ cancers, including cancers of the liver, pancreas, lungs, and kidneys. It is a valuable molecule involved in cancer cell adhesion, invasion, spreading, angiogenesis, complement inhibition, and signaling. Although the biological significance underlying NG2/CSPG4 proteoglycan involvement in cancer progression needs to be better defined, based on the current evidence, NG2/CSPG4+ cells, such as pericytes (PCs, NG2+/CD146+/PDGFR-β+) and cancer stem cells (CSCs), are closely associated with the liver malignancy, hepatocellular carcinoma (HCC), pancreatic malignancy, and pancreatic ductal adenocarcinoma (PDAC) as well as poor prognoses. Importantly, with a unique method, we successfully purified NG2/CSPG4-expressing cells from human HCC and PDAC vasculature tissue blocks (by core needle biopsy). The cells appeared to be spheres that stably expanded in cultures. As such, these cells have the potential to be used as sources of target antigens. Herein, we provide new information on the possibilities of frequently selecting NG2/CSPG4 as a solid organ cancer biomarker or exploiting expressing cells such as CSCs, or the PG/chondroitin sulfate chain of NG2/CSPG4 on the cell membrane as specific antigens for the development of antibody- and vaccine-based immunotherapeutic approaches to treat these cancers.

New advances of NG2-expressing cell subset in marrow mesenchymal stem cells as novel therapeutic tools for liver fibrosis/cirrhosis

“…Figs. S1 C; S3 E) [ 48 ], which is consistent with the characteristics reported in the literature [ 7 ]. However, whether NG2 + cells can generate multiple cell types is currently unclear.…”

Neuron-Glial Antigen 2 Participates in Liver Fibrosis via Regulating the Differentiation of Bone Marrow Mesenchymal Stem Cell to Myofibroblast

“…For instance, genetic mutation of CSPG4 led to the dysfunction of oligodendrocyte progenitor cells and failure to differentiate into myelinating oligodendrocytes in familial schizophrenia [ 15 ]. Recent studies have identified that NG2 functions in various cell types and NG2 levels are increased in many aggressive cancers, including melanomas [ 16 ], gliomas [ 17 ], mesotheliomas [ 18 ], sarcomas [ 19 ], anaplastic thyroid cancer [ 20 ], triple-negative breast cancers [ 21 ] and hepatocellular carcinoma [ 22 ]. Moreover, NG2 overexpression may induce highly aggressive tumors characterized by increased angiogenesis and a moderately invasive phenotype [ 23 , 24 ].…”

RNA methylation patterns mediated by m 6 A regulators are involved in the regulation of immune microenvironment in hepatocellular carcinoma

“…Although multiple therapeutic approaches such as surgical and operative excision, radiotherapy and chemotherapy have been applied in the treatment of this disease, the treatment effect is not satisfactory, which leads a poor prognosis [4]. Recently, a promising therapeutic strategy named as immunotherapy is pointed, and proves to be effective against solid organ cancers including HCC under laboratory conditions [5,6]. However, the well understanding of the changes in immune microenvironment during HCC is still urgent, which may contribute to identify novel and e cient Immunotherapeutic targets.…”