Functional and Clinical Relevance of Chondroitin Sulfate Proteoglycan 4

Campoli, Michael; Ferrone, Soldano; Wang, Xinhui

doi:10.1016/b978-0-12-380890-5.00003-x

Cited by 97 publications

(108 citation statements)

References 160 publications

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“…In particular, human CSPG4 (hCSPG4) displays 82% homology and 88% similarity to its canine counterpart in its amino-acidic sequence. Moreover, the frequency of CSPG4 expression in canine and human melanoma lesions is quite similar, being about 60% (19) and 80% (20), respectively. DNA vaccination has been extensively explored in the field of melanoma immunotherapy, and a number of DNA vaccination clinical trials have been performed in human patients with melanoma; trial results have all been disappointing, probably because of the lack of immunogenicity in DNA vaccines, even when administered with Salmonella typhimurium (21)(22)(23)(24).…”

Section: Introductionmentioning

confidence: 81%

“…A cause-effect relationship between the induction of a CSPG4-specific immune response and a statistically significant DFI and survival prolongation has not been proved in either patients with human or canine melanoma. Nevertheless, CSPG4-specific mAb have been shown to inhibit the proliferation and migration of melanoma cells in vitro (20). Furthermore, CSPG4-specific mAb administration to SCID mice grafted with CSPG4-positive human tumors has been found to significantly prolong their survival.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, CSPG4-specific mAb administration to SCID mice grafted with CSPG4-positive human tumors has been found to significantly prolong their survival. These effects reflect the inhibition by CSPG4-specific mAb of signaling pathways associated with cell proliferation (20).…”

Section: Discussionmentioning

confidence: 99%

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CSPG4-Specific Immunity and Survival Prolongation in Dogs with Oral Malignant Melanoma Immunized with Human CSPG4 DNA

Riccardo¹,

Iussich

Maniscalco

et al. 2014

Clinical Cancer Research

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Purpose: Due to the many similarities with its human counterpart, canine malignant melanoma (cMM) is a valuable model in which to assess the efficacy of novel therapeutic strategies. The model is herein used to evaluate the immunogenicity, safety, and therapeutic efficacy of a human chondroitin sulfate proteoglycan-4 (hCSPG4) DNA-based vaccine. The fact that homology between hCSPG4 and cCSPG4 amino-acidic sequences stands at more than 80% provides the rationale for using an hCSPG4 DNA vaccine in the cMM model.Experimental Design: Dogs with stage II-III surgically resected CSPG4-positive oral MM were subjected to monthly intramuscular plasmid administration, which was followed immediately by electroporation (electrovaccination) for at least 6, and up to 20, months. The immunogenicity, safety, and therapeutic efficacy of the vaccine have been evaluated.Results: hCSPG4 electrovaccination caused no clinically relevant local or systemic side effects and resulted in significantly longer overall and disease-free survival times in 14 vaccinated dogs as compared with 13 nonvaccinated controls. All vaccinated dogs developed antibodies against both hCSPG4 and cCSPG4. Seven vaccinated dogs were also tested for a cCSPG4-specific T-cell response and only two gave a detectable interferon (IFN)g response.Conclusion: Xenogeneic electrovaccination against CSPG4 is able to overcome host unresponsiveness to the "self" antigen and seems to be effective in treating cMM, laying the foundation for its translation to a human clinical setting.

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Section: Introductionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

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CSPG4-Specific Immunity and Survival Prolongation in Dogs with Oral Malignant Melanoma Immunized with Human CSPG4 DNA

Riccardo¹,

Iussich

Maniscalco

et al. 2014

Clinical Cancer Research

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“…Gao et al, 2010;Qiao et al, 2011;Kejner et al, 2013 Chondroitin sulfate proteoglycan 4 (CSPG4) -CSPG4 is a unique glycoprotein proteoglycan complex that has been implicated in melanoma, sarcoma and various carcinomas. Campoli et al, 2010;Wang et al, 2010 CXCR4 -CXCR4 is a chemokine receptor found to play an important role in several cancers.…”

Section: Sabine Et Al 2008)mentioning

confidence: 99%

Cancer Stem Cells and Stemness Markers in Oral Squamous Cell Carcinomas

Patel¹,

Shah²,

Shah³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…Likewise, a chondroitin sulfate (CS)−containing proteoglycan called CSPG4 is also present on CSCs and is involved in regulating cell proliferation, migration, and angiogenesis. 15 Although HS and CS play major roles in growth and differentiation of CSCs, they also contribute to bulk tumor cell biology. 3 This implies selective targeting of CSCs through GAG modulation can be expected to be difficult from the perspective of competing GAG modulation of bulk tumor cells also.…”

mentioning

confidence: 99%

395 Synthetic, Non-Saccharide Glycosaminoglycan Mimetics Selectively Target Colon Cancer Stem Cells

Patel¹,

Karuturi²,

Al‐Horani³

et al. 2014

Gastroenterology

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Selective targeting of cancer stem-like cells (CSCs) is a paradigm-shifting approach. We hypothesized that CSCs can be targeted by interfering with functions of sulfated glycosaminoglycans, which play key roles in cancer cell growth, invasion and metastasis. We developed a tandem, dual screen strategy involving (1) assessing inhibition of monolayer versus spheroid growth and (2) assessing inhibition of primary versus secondary spheroid growth to identify G2.2, a unique sulfated nonsaccharide GAG mimetic (NSGM) from a focused library of 53 molecules, as a selective inhibitor of colon CSCs. The NSGM down-regulated several CSC markers through regulation of gene transcription, while closely related, inactive NSGMs G1.4 and G4.1 demonstrated no such changes. G2.2's effects on CSCs were mediated, in part, through induction of apoptosis and inhibition of self-renewal factors. Overall, this work presents the proof-of-principle that CSCs can be selectively targeted through novel NSGMs, which are likely to advance fundamental understanding on CSCs while also aiding development of novel therapeutic agents.

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Functional and Clinical Relevance of Chondroitin Sulfate Proteoglycan 4

Cited by 97 publications

References 160 publications

CSPG4-Specific Immunity and Survival Prolongation in Dogs with Oral Malignant Melanoma Immunized with Human CSPG4 DNA

CSPG4-Specific Immunity and Survival Prolongation in Dogs with Oral Malignant Melanoma Immunized with Human CSPG4 DNA

Cancer Stem Cells and Stemness Markers in Oral Squamous Cell Carcinomas

395 Synthetic, Non-Saccharide Glycosaminoglycan Mimetics Selectively Target Colon Cancer Stem Cells

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