C-Met as a Key Factor Responsible for Sustaining Undifferentiated Phenotype and Therapy Resistance in Renal Carcinomas
Abstract
:1. Introduction
2. C-Met Receptor
3. C-Met Receptor and Kidney Tumors
3.1. C-Met is Associated with an Advanced Stage and Poor Survival of Patients
3.2. Germline and Somatic Mutations of C-Met Receptor in Renal Carcinomas
3.3. Phosphorylation of C-Met in Renal Carcinomas
4. Resistance to Anti-Cancer Therapies in RCC
4.1. C-Met Receptor and Therapy Resistance
4.2. Epithelial to Mesenchymal Transition in the Acquisition of Therapeutic Resistance
5. C-Met Receptor as a Marker of Undifferentiated Cells
6. Conclusions
Funding
Acknowledgments
Conflicts of Interest
References
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Study (Year) | Type | c-Met Detection Method | Expression c-Met (Number Positive/Number Tested) | c-Met Expression in Percent | Major Conclusion |
---|---|---|---|---|---|
Natali et al. (1996) [23] | RCC | Immunohist-ochemical (IHC) | 39/45 | 87% | - increased expression at various levels in kidney cells of tumors with different histological and cytological properties; - c-Met may be involved in the formation and progression of renal cancer cells; |
Pisters et al. (1997) [31] | Papillary cell | IHC | 3/3 | 68% | - high expression of c-Met in renal cell carcinomas; - correlation between the higher level of c-Met and higher nuclear grade renal cancers; |
Mixed clear and granular cell | 24/37 | ||||
Rhabdoid/sarcomatoid | 1/1 | ||||
Oncocytoma | IHC | 8/8 | 100% | ||
Sweeney et al. (2002) [45] | Papillary renal carcinoma | IHC | 40/50 | 80% | 20% of papillary cancers did not express c-Met—another possible mechanism responsible for tumorigenesis; - correlation of the growing stage of cancer with c-Met expression; - a tendency for higher overall survival in patients with c-Met -negative tumors; |
Jong Sun Choi et al. (2006) [33] | Conventional renal carcinoma | IHC | 43/96 | 45% | - significant relationship between c-Met expression and high nuclear level, as well as several clinical–pathological parameters, which indicates tumor invasion or aggressiveness; - the ability to distinguish between RCC subtypes by diffuse and strong immunoexpression of c-Met in RCC and collecting duct carcinomas as compared to subtypes with tubulo-papillary growth; |
Papillary renal carcinoma | 18/20 | 90% | |||
Chromophobe renal carcinoma | 2/24 | 8% | |||
Collecting duct carcinoma | 5/5 | 100% | |||
Urothelial carcinoma of renal pelvis | 23/25 | 92% | |||
Oncocytoma | 0/12 | 0% | |||
Miyata et al. (2006) [24] | RCC | IHC | 73/114 | 64% | - detection of pY1349 c-Met expression is an excellent predictor for the prognosis of patients with sporadic conventional RCC because it is positively associated with tumor grade, stage and size as well as cancer cell proliferation in patients; |
Gontero et al. (2008) [46] | Papillary renal carcinoma | IHC | 13/46 | 29% | - positive c-Met expression was significantly more common in papillary RCC (PRCC) type 2 (p < 0.001), however lack of correlation with multifocal kidney disease (p = 0.86) and occurrence of metachronous tumors (p = 0.93); - c-Met expression had no prognostic value; |
Mukai et al. (2015) [47] | RCC | IHC | 8/17 | 47% | - high c-Met and matriptase expression was found in RCC cells that had metastasized to bone and was accompanied by matriptase expression in osteoclasts, which indicates a significant role for these molecules in bone metastasis; |
Macher-Goeppinger et al. (2017) [35] | ccRCC | IHC and CISH analyses | 476/572 | 83% | - high expression of c-Met and MET copy number gains was associated with clinical and pathological features in the primary tumor, an aggressive phenotype and an unfavorable patient outcome; - c-Met expression and MET copy number should be used in relapses or metastases to target anti c-Met therapy in patients with ccRCC; |
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Marona, P.; Górka, J.; Kotlinowski, J.; Majka, M.; Jura, J.; Miekus, K. C-Met as a Key Factor Responsible for Sustaining Undifferentiated Phenotype and Therapy Resistance in Renal Carcinomas. Cells 2019, 8, 272. https://doi.org/10.3390/cells8030272
Marona P, Górka J, Kotlinowski J, Majka M, Jura J, Miekus K. C-Met as a Key Factor Responsible for Sustaining Undifferentiated Phenotype and Therapy Resistance in Renal Carcinomas. Cells. 2019; 8(3):272. https://doi.org/10.3390/cells8030272
Chicago/Turabian StyleMarona, Paulina, Judyta Górka, Jerzy Kotlinowski, Marcin Majka, Jolanta Jura, and Katarzyna Miekus. 2019. "C-Met as a Key Factor Responsible for Sustaining Undifferentiated Phenotype and Therapy Resistance in Renal Carcinomas" Cells 8, no. 3: 272. https://doi.org/10.3390/cells8030272