Chondroitin Sulfate Proteoglycan 4 as a Marker for Aggressive Squamous Cell Carcinoma
Abstract
:Simple Summary
Abstract
1. Introduction
2. Need for Markers of Malignant SCC
3. Structure and Function of CSPG4
3.1. CSPG4/NG2 Structure
3.2. CSPG4 Function in Malignancy
3.2.1. Regulation of Extracellular Proteases
3.2.2. CSPG4 as a Co-Receptor
3.2.3. CSPG4 & Integrin Signalling
3.2.4. CSPG4 as a Receptor for Structural Components of the ECM
3.2.5. c-Met, CSPG4 and the EMT
3.2.6. CSPG4 & Angiogenesis
4. CSPG4 Expression in Disease and Development
4.1. An Overview of Methodological Approach
4.2. Tissue Distribution of CSPG4
4.3. CSPG4 Expression in Malignancy
4.4. CSPG4 Expression, Patient Survival & Stage
5. Genes Co-Regulated with CSPG4 in SCCs
5.1. CSPG4 Co-Expressed Genes in HNSCC and cSCC
5.2. Comparison with Results of Single Cell Analysis
5.3. CSPG4 Co-Expressed Genes in RDEB SCCs
5.4. Skin Stem Cells, the p-EMT/TSK Programs and CSPG4
6. CSPG4 as a Diagnostic Marker in Cancer
7. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Author/Source | Cell/Tissue/Organ Type | Protein Levels | Median Expression ** | Type (A/E) * | ||
---|---|---|---|---|---|---|
The Human Protein Atlas and Uhlén et al. [49] Huret et al. [50] | Brain | Cerebral cortex | High | A | ||
Cerebellum | High | |||||
Hippocampus | High | |||||
Caudate | Medium | |||||
Endocrine | Thyroid | Medium | A | |||
Parathyroid | Medium | |||||
Adrenal gland | Medium | |||||
Respiratory | Nasopharynx | High | A | |||
Bronchus | High | |||||
Lung | Medium | |||||
Proximal digestive tract | Oral mucosa | Low | A | |||
Salivary gland | Medium | |||||
Esophagus | Medium | |||||
Gastrointestinal tract | Stomach | Medium | A | |||
Duodenum | High | |||||
Small intestine | High | |||||
Colon | Medium | |||||
Rectum | Medium | |||||
Liver | Medium | A | ||||
Gallbladder | High | A | ||||
pancreas | High | A | ||||
Kidney | Medium | A | ||||
Bladder | Medium | A | ||||
Male reproductive organs | Medium | A | ||||
Female reproductive organs | Vagina | Medium | ||||
Ovary | Medium | |||||
Fallopian tube | Medium | |||||
Endometrium | High | |||||
Cervix | Medium | |||||
Placenta | Medium | |||||
Breast | Medium | |||||
Muscle | Heart muscle | Medium | A | |||
Smooth | Low | |||||
Skeletal | Medium | |||||
Adipose tissue and soft tissue | Low-Medium | A | ||||
Skin | Medium | A | ||||
Lymphoid tissue | Bone marrow | Medium | A | |||
Appendix | High | |||||
Spleen | Medium | |||||
Lymph node | Medium | |||||
Tonsil | Medium | |||||
Haematopoietic | Low | A | ||||
*** GTEx data, Carithers et al. [51] | Lung | 37.81 | A | |||
Vascular | Aorta | 175.6 | ||||
Coronary artery | 132.6 | |||||
Tibial artery | 246.2 | |||||
Heart | Atrial appendage | 12.85 | ||||
Left ventricle | 8.040 | |||||
Brain | Amygdala | 10.48 | ||||
Anterior cingulate cortex | 8.864 | |||||
Caudate | 6.361 | |||||
Cerebellar hemisphere | 3.078 | |||||
Cerebellum | 3.845 | |||||
Cortex | 7.710 | |||||
Frontal cortex | 6.361 | |||||
Hippocampus | 8.213 | |||||
Hypothalamus | 8.861 | |||||
Nucleus accumbens | 6.160 | |||||
Putamen | 5.692 | |||||
Spinal cord | 5.574 | |||||
Substantia nigra | 8.926 | |||||
Nerve (tibial) | 66.59 | |||||
Pituitary | 2.565 | |||||
Thyroid | 11.30 | |||||
Liver | 0.5535 | |||||
Pancreas | 1.326 | |||||
Spleen | 9.568 | |||||
Stomach | 10.87 | |||||
Small intestine | 10.92 | |||||
Colon | Sigmoid | 105.7 | ||||
Transverse | 35.10 | |||||
Esophagus | Gastroesophageal junction | 98.16 | ||||
Mucosa | 7.547 | |||||
Muscularis | 98.31 | |||||
Cervix | Ectocervix | 29.65 | ||||
Endocervix | 28.90 | |||||
Female reproductive organs | Fallopian tube | 37.31 | ||||
Ovary | 12.14 | |||||
Uterus | 60.30 | |||||
Vagina | 19.53 | |||||
Breast | 23.63 | |||||
Male reproductive organs | Prostate | 23.09 | ||||
Testis | 3.153 | |||||
Kidney | Medulla | 6.372 | ||||
Cortex | 4.208 | |||||
Adrenal gland | 2.933 | |||||
Bladder | 59.06 | |||||
Adipose | Subcutaneous | 51.61 | ||||
Visceral | 33.41 | |||||
Skeletal muscle | 23.65 | |||||
Fibroblasts (cultured) | 14.35 | |||||
Skin | Sun exposed | 13.22 | ||||
Non sun exposed | 10.93 | |||||
Whole blood | 0.09142 | |||||
Nishiyama et al. [136] | Chondroblast precursors | E | ||||
Fukushi et al. [48] | Chondroblast precursors | E | ||||
Osteoblast precursors | ||||||
Ozerdem et al. [54], Grako et al. [137] | Cardiomyocytes | E | ||||
Pericytes | E & A | |||||
Vascular smooth muscle | E | |||||
Midwood et al. [138] | Chondrocytes | A | ||||
Ghali et al. [139] | Epidermal and interfollicular progenitor cells | A | ||||
Legg et al. [140], Giangreco et al. [141] | Interfollicular epidermis progenitor cells | A | ||||
Schiffer et al. [123] | Oligodendrocyte precursor cells | A | ||||
Trotter et al. [142] | Oligodendrocyte precursor cells | A | ||||
Protoplasmic astrocytes | ||||||
Neurons | ||||||
Kozanoglu et al. [143] | Bone marrow mesenchymal cells | A |
Author/Source | Tumour Type | % CSPG4+ Lesions Compared to Total | Rel. Expression Compared to Normal | |
---|---|---|---|---|
Wilson et al. [57] | Melanoma | 98.3–100% | ||
NMSC | cSCC | 37.5–50% | ||
Basal cell carcinoma | ||||
Nishi et al. [146] | Melanoma | Acral lentigous melanoma (ALM) | 53.6% | Increased; staining intensity for ALM was weaker than SSM |
Superficial spreading melanoma (SSM) | 100% | |||
Kageshita et al. [147] | Melanoma | Primary | 50% | |
Metastatic | 83.3% | |||
Beard et al. [148] | Melanoma | Increased | ||
Triple Negative breast Cancer (TNBC) | Increased | |||
Glioblastoma | Increased | |||
Tang et al. [47] | Pancreatic adenocarcinoma | Increased | ||
Pheochromocytoma and paraganglioma | ||||
Esophageal carcinoma | ||||
HNSCC | ||||
Brain lower grade glioma | ||||
Glioblastoma multiforme | ||||
Kidney renal clear cell carcinoma | ||||
Melanoma | ||||
Uhlen et al. [49] | Renal cancer | |||
Urothelial cancer | ||||
Glioma | ||||
Warta et al. [134] | HNSCC | Increased | ||
Schwab et al. [149] | Chordoma and chondrosarcoma | Present | ||
Wang et al. [150] | Breast cancer | ER−/PR−/HER2−(TNBC) | 72.7% | |
ER+ | 28.6% | |||
HER2+ | 16.7% | |||
Behm et al. [131] | Acute lymphoblastic leukemia | 8.6% | ||
Petrovici et al. [130] | Acute myeloid leukemia | 50% | ||
Rivera et al. [151] | Malignant mesothelioma | 60.98% | ||
Keleg et al. [129] | Pancreatic carcinoma | Adenosquamous carcinoma | Increased | |
Anaplastic ductal adenocarcinoma | ||||
Intraductal papillary mucinous neoplasm with associated invasive carcinoma | ||||
Riccardo et al. [152] | Osteosarcoma | Increased |
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Chen, K.; Yong, J.; Zauner, R.; Wally, V.; Whitelock, J.; Sajinovic, M.; Kopecki, Z.; Liang, K.; Scott, K.F.; Mellick, A.S. Chondroitin Sulfate Proteoglycan 4 as a Marker for Aggressive Squamous Cell Carcinoma. Cancers 2022, 14, 5564. https://doi.org/10.3390/cancers14225564
Chen K, Yong J, Zauner R, Wally V, Whitelock J, Sajinovic M, Kopecki Z, Liang K, Scott KF, Mellick AS. Chondroitin Sulfate Proteoglycan 4 as a Marker for Aggressive Squamous Cell Carcinoma. Cancers. 2022; 14(22):5564. https://doi.org/10.3390/cancers14225564
Chicago/Turabian StyleChen, Kathryn, Joel Yong, Roland Zauner, Verena Wally, John Whitelock, Mila Sajinovic, Zlatko Kopecki, Kang Liang, Kieran Francis Scott, and Albert Sleiman Mellick. 2022. "Chondroitin Sulfate Proteoglycan 4 as a Marker for Aggressive Squamous Cell Carcinoma" Cancers 14, no. 22: 5564. https://doi.org/10.3390/cancers14225564