CSPG4 Protein as a New Target for the Antibody-Based Immunotherapy of Triple-Negative Breast Cancer

Wang, Xinhui; Osada, Takuya; Wang, Yangyang; Yu, Ling; Sakakura, Koichi; Katayama, Akihiro; McCarthy, James B.; Brufsky, Adam; Chivukula, Mamatha; Khoury, Thaer; Hsu, David S.; Barry, William T.; Lyerly, H. Kim; Clay, Timothy M.; Ferrone, Soldano

doi:10.1093/jnci/djq343

Cited by 154 publications

(202 citation statements)

References 72 publications

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“…CSPG4 is considered a prominent CSPG with a tumor promoting role. patients with aggressive breast cancer falls in line with our data (Wang et al, 2010a;Wang et al, 2010b). However, targeting a core protein may bring in specificity issues as these PGs are also expressed in stroma.…”

Section: Diagnostic and Therapeutic Valuessupporting

confidence: 87%

On the Role of Cell Surface Chondroitin Sulfates and Their Core Proteins in Breast Cancer Metastasis

Kieber-Emmons¹,

Jousheghany²,

Monzavi‐Karbassi³

2011

Breast Cancer - Focusing Tumor Microenvironment, Stem Cells and Metastasis

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Section: Diagnostic and Therapeutic Valuessupporting

confidence: 87%

On the Role of Cell Surface Chondroitin Sulfates and Their Core Proteins in Breast Cancer Metastasis

Kieber-Emmons¹,

Jousheghany²,

Monzavi‐Karbassi³

2011

Breast Cancer - Focusing Tumor Microenvironment, Stem Cells and Metastasis

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“…However, the proteoglycan is also expressed by tumor cells in several types of cancer, including melanoma, [41][42][43][44] glioblastoma, 38,45,46 sarcoma, 47 myeloid leukemia, 48 and triple-negative breast cancer. 49 In all cases, increased NG2 expression by tumor cells is associated with enhanced tumor progression and worsened patient prognosis. Tumor cell NG2 promotes neoplastic progression by enhancing tumor cell proliferation, motility, and survival via enhanced integrin and growth factor signaling.…”

Section: Discussionmentioning

confidence: 99%

NG2 proteoglycan-dependent recruitment of tumor macrophages promotes pericyte-endothelial cell interactions required for brain tumor vascularization

et al. 2015

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Early stage growth of intracranial B16F10 tumors is reduced by 87% in myeloid-specific NG2 null (Mac-NG2ko) mice and by 77% in pericyte-specific NG2 null (PC-NG2ko) mice, demonstrating the importance of the NG2 proteoglycan in each of these stromal compartments. In both genotypes, loss of pericyte-endothelial cell interaction results in numerous structural defects in tumor blood vessels, including decreased formation of endothelial cell junctions and decreased assembly of the vascular basal lamina. All vascular deficits are larger in Mac-NG2ko mice than in PC-NG2ko mice, correlating with the greater decrease in pericyte-endothelial cell interaction in Mac-NG2ko animals. Accordingly, tumor vessels in Mac-NG2ko mice have a smaller diameter, lower degree of patency, and higher degree of leakiness than tumor vessels in PC-NG2ko mice, leading to less efficient tumor blood flow and to increased intratumoral hypoxia. While reduced pericyte interaction with endothelial cells in PC-NG2ko mice is caused by loss of NG2-dependent pericyte activation of b1 integrin signaling in endothelial cells, reduced pericyte-endothelial cell interaction in MacNG2ko mice is due to a 90% reduction in NG2-dependent macrophage recruitment to tumors. The absence of a macrophage-derived signal(s) in Mac-NG2ko mice results in the loss of pericyte ability to associate with endothelial cells, possibly due to reduced expression of N-cadherin by both pericytes and endothelial cells.

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“…The cell surface proteoglycan chondroitin sulfate proteoglycan 4 (CSPG4) was detected on breast carcinoma cells from primary carcinomas and malignant pleural effusions, and in the latter specimens was observed on CSC with a CD44 + /CD24 low/- profile by FC [49]. …”

Section: Fc In Effusion Researchmentioning

confidence: 99%

Malignant Nonhematological Effusion Characterization by Flow Cytometry

Davidson

2016

Acta Cytologica

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With the exception of hematological malignancies, flow cytometry (FC) is infrequently applied as an ancillary tool in the diagnosis of malignant effusions in most institutions. However, FC may be effectively used to differentiate between epithelial cells, mesothelial cells and leukocytes using antibodies against both cell surface and intracellular proteins, offering the advantage of quantitative analysis. Additionally, FC may be applied to the quantitative detection of cancer-associated molecules, including stem cell markers, as well as assessment of critical cellular processes, such as proliferation and apoptosis. Some of the latter tests may have relevance for monitoring treatment response in the presence of metastatic disease, although this does not constitute routine practice to date. This review summarizes current knowledge regarding the application of FC to serous effusions in the diagnostic setting, as well as in research into cancer biology focusing on clinical specimens. The studies published to date suggest a role for this method in the clinical setting in the context of diagnosis, prediction and prognosis.

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CSPG4 Protein as a New Target for the Antibody-Based Immunotherapy of Triple-Negative Breast Cancer

Abstract: This study identified CSPG4 as a new target for TNBC. The antitumor activity of CSPG4-specific mAb was mediated by multiple mechanisms, including the inhibition of signaling pathways crucial for TNBC cell survival, proliferation, and metastasis.

Cited by 154 publications

References 72 publications

On the Role of Cell Surface Chondroitin Sulfates and Their Core Proteins in Breast Cancer Metastasis

On the Role of Cell Surface Chondroitin Sulfates and Their Core Proteins in Breast Cancer Metastasis

NG2 proteoglycan-dependent recruitment of tumor macrophages promotes pericyte-endothelial cell interactions required for brain tumor vascularization

Malignant Nonhematological Effusion Characterization by Flow Cytometry

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