Theranostic Impact of NG2/CSPG4 Proteoglycan in Cancer

Abstract

NG2/CSPG4 is an unusual cell-membrane integral proteoglycan widely recognized to be a prognostic factor, a valuable tool for ex vivo and non-invasive molecular diagnostics and, by virtue of its tight association with malignancy, a tantalizing therapeutic target in several tumour types. Although the biology behind its involvement in cancer progression needs to be better understood, implementation of NG2/CSPG4 in the routine clinical practice is attainable and has the potential to contribute to an improved individualized management of cancer patients. In this context, its polymorphic nature seems to be particularly valuable in the effort to standardize informative diagnostic procedures and consolidate forcible immunotherapeutic treatment strategies. We discuss here the underpinnings for this potential and highlight the benefits of taking advantage of the intra-tumour and inter-patient variability in the regulation of NG2/CSPG4 expression. We envision that NG2/CSPG4 may effectively be exploited in therapeutic interventions aimed at averting resistance to target therapy agents and at interfering with secondary lesion formation and/or tumour recurrence.

Disruption of lineage specification in adult pulmonary mesenchymal progenitor cells promotes microvascular dysfunction

“…In the WT MPCs, we detected NG2 as a single band, while multiple bands were present at varying intensities in the βOE and Bmpr2 fl/+ MPCs ( Figure 2B). These multiple bands are the result of extracellular processing of the NG2 proteoglycan that may then regulate signaling as well as migration (31). We again identified increased gene and protein expression of the Wnt/β-catenin target WNT1-inducible signaling pathway protein 1 (Wisp1) (Figure 2, A Figure 4H), which is associated with pericyte or endothelial lineage specification from MPCs (33,34).…”

Increased NG2 and SOX2 expression is associated with high-grade choroid plexus tumors

“…To the best of our knowledge there are no previous studies investigating NG2 or SOX2 expression levels in CPTs but they have been previously associated with cancer development (15)(16)(17)(18)(19)(20)(21)(22). Increased expression of NG2 has been demonstrated in a variety of head and neck cancers, glioma and pituitary cells (15)(16)(17)(18).…”

“…Increased expression of NG2 has been demonstrated in a variety of head and neck cancers, glioma and pituitary cells (15)(16)(17)(18). SOX2 overexpression or gene amplification has been associated with the development of lung, esophageal, breast and gastric cancers (19-22).…”

Proteoglycans in normal physiology and carcinogenesis

“…Нервный глиальный антиген 2 (NG2/CSPG4) -транс-мембранный ПГ, несущий цепи ХС и имеющий крупный внеклеточный домен, содержащий 3 субдо-мена, среди которых N-терминальный домен содержит 2 ламининподобных повтора [19]. По-видимому, лами-нинподобные домены опосредуют связывание лигандов, межклеточные взаимодействия и взаимодействия кле-ток с окружающим ВКМ, а также взаимодействие с ин-тегринами и рецепторами тирозинкиназ.…”

“…NG2/CSPG4 является прогностическим фактором и инструментом неинвазивной молекулярной диа-гностики благодаря тесной ассоциации со злокаче-ственными новообразованиями, а также может быть терапевтической мишенью в некоторых типах опухо-лей [19].…”