Prostat Adenokarsinomunun Tanısında ve Prognostik Sınıflandırmasında CCR3 Ekspresyonunun Prediktif Değeri
Yıl 2022,
Cilt: 11 Sayı: 3, 440 - 446, 04.10.2022
Ayla Solmaz Avcıkurt
,
Eren Altun
,
Fatma Bahar Sunay
Öz
Amaç: Kemokinler, enflamatuar ve immünolojik bir reaksiyonu indüklemek için hasarlı veya enfekte dokulardan salgılanan faktörlerdir. Hem kemokinler hem de reseptörleri, tümör oluşumunun kritik aktörleri olarak kabul edilir. Çalışmamız, prostat adenokarsinomunda (PCa) son zamanlarda çoğu kanser hücresi tarafından salgılandığı tespit edilen bir kemokin reseptörü olan CCR-3 ekspresyonunu araştırmayı ve Gleason prognostik derecesi ile CCR-3 seviyeleri arasındaki olası ilişkiyi ortaya koymayı amaçlamaktadır. Gereç ve Yöntem: Çalışmaya, prostatektomi yapılan PCa'lı 25 hasta ve iyi huylu prostat hiperplazisi (BPH) olan 25 hasta dahil edildi. Her iki hasta grubunda da CCR-3 ekspresyonu hem Real-Time PCR ile mRNA düzeyinde, hem de immünohistokimyasal (IHC) boyama ile protein düzeyinde saptandı. PCa ve BPH gruplarının sonuçları karşılaştırıldı. PCa grubunda CCR-3 ekspresyonu ile Gleason prognostik derecesi arasında herhangi bir ilişki de araştırıldı. Bulgular: Her ne kadar PCa hastalarında CCR-3 ekspresyonu mRNA düzeyinde anlamlı olarak yüksek bulunduysa da (p=0.001), fark protein düzeyinde anlamlı değildi (p=0.205). Yine, farklı Gleason prognostik derecelerine sahip hastaların CCR3 ekspresyon seviyeleri arasındaki fark hem mRNA hem de protein seviyelerinde anlamlı değildi. PCa hastalarında CCR-3 IHC boyaması ile toplam PSA düzeyleri (p=0.001) arasında istatistiksel olarak anlamlı pozitif korelasyon bulundu. Sonuç: CCR-3 mRNA düzeylerinin PCa tanısında faydalı olabileceği sonucuna varıldı.
Proje Numarası
BAP. 2017/201
Kaynakça
- Alizadeh, A. M., Shiri, S., Farsinejad, S. (2014). Metastasis review: from bench to bedside. Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine, 35(9), 8483-8523. https://doi.org/10.1007/s13277-014-2421-z
- Andalib, A., Doulabi, H., Maracy, M. R., Rezaei, A., & Hasheminia, S. J. (2013). CCR3, CCR4, CCR5, and CXCR3 expression in peripheral blood CD4+ lymphocytes in gastric cancer patients. Advanced Biomedical Research, 2, 31. https://doi.org/10.4103/2277-9175.108770
- Araújo, J. M. D., Silva, L. A. S., Felix, F. B., Camargo, E. A., & Grespan, R. (2020). CCR3 antagonist impairs estradiol-induced eosinophil migration to the uterus in ovariectomized mice. Brazilian Journal of Medical and Biological Research, 53(1), Article e8659. http://doi.org/10.1590/1414-431X20198659
- Balkwill, B. (2004). Cancer and the chemokine network. Nature Reviews. Cancer, 4(7), 540–550. https://doi.org/10.1038/nrc1388
- Bostwick, D.G., Burke, H.B., Djakiew, D., Euling, S., Ho, S., Landolph, J., Morrison, H., Sonawane, B., Shifflett, T., Waters, D. J., & Timmset, B. (2004). Human prostate cancer risk factors. Cancer, 101(10 Suppl), 2371–2490. https://doi.org/10.1002/cncr.20408
- Castillejos-Molina, R. A., & Gabilondo-Navarro, F. B. (2016). Prostate cancer. Salud publica de Mexico, 58(2), 279–284. https://doi.org/10.21149/spm.v58i2.7797
- Coussens, L. M., & Werb, Z. (2002). Inflammation and cancer. Nature, 420(6917), 860–867. https://doi.org/10.1038/nature01322
- Cuzick, J., Thorat, M. A., Andriole, G., Brawley, O. W., Brown, P. H., Culig, Z., Eeles, R. A., Ford, L. G., Hamdy, F. C., Holmberg, L., Ilic, D., Key, T. J., La Vecchia, C., Lilja, H., Marberger, M., Meyskens, F. L., Minasian, L. M., Parker, C., Parnes, H. L., Perner, S., … Wolk, A. (2014). Prevention and early detection of prostate cancer. The Lancet. Oncology, 15(11), e484–e492. https://doi.org/10.1016/S1470-2045(14)70211-6
- Demirel, C. & Kılçıksız S. (2011). Asetil salisilik asitin radyokoruyucu etkisi. Türk Onkoloji Dergisi, 26(1), 45–53. http://doi.org/10.5505/tjoncol.2011.546
- Epstein, J. I., Egevad, L., Amin, M. B., Delahunt, B., Srigley, J. R., Humphrey, P. A., & Grading Committee (2016a). The 2014 International Society of Urological Pathology (ISUP) consensus conference on Gleason grading of prostatic carcinoma: Definition of grading patterns and proposal for a new grading system. The American Journal of Surgical Pathology, 40(2), 244–252. https://doi.org/10.1097/PAS.0000000000000530
- Epstein, J. I., Zelefsky, M. J., Sjoberg, D. D., Nelson, J. B., Egevad, L., Magi-Galluzzi, C., Vickers, A. J., Parwani, A. V., Reuter, V. E., Fine, S. W., Eastham, J. A., Wiklund, P., Han, M., Reddy, C. A., Ciezki, J. P., Nyberg, T., & Klein, E. A. (2016b). A contemporary prostate cancer grading system: A validated alternative to the Gleason score. European Urology, 69(3), 428–435. https://doi.org/10.1016/j.eururo.2015.06.046
- Guan, X. (2015). Cancer metastases: challenges and opportunities. Acta Pharmaceutica Sinica B, 5(5), 402–418. https://doi.org/10.1016/j.apsb.2015.07.005
- Kleinhans, M., Tun-Kyi, A., Gilliet, M., Kadin, M. E., Dummer, R., Burg, G., & Nestle, F. O. (2003). Functional expression of the eotaxin receptor CCR3 in CD30+ cutaneous T-cell lymphoma. Blood, 101(4), 1487–1493. https://doi.org/10.1182/blood-2002-02-0475
- Kumar, V., Abbas A. K., & Aster, J. C. (2014). Robbins Basic Pathology (9th ed. ). W. B. Saunders Company.
Legler, D. F., & Thelen, M. (2018). New insights in chemokine signaling. F1000Research, 7, 95. https://doi.org/10.12688/f1000research.13130.1
- Laurent, V., Guérard, A., Mazerolles, C., Le Gonidec, S., Toulet, A., Nieto, L., Zaidi, F., Majed, B., Garandeau, D., Socrier, Y., Golzio, M., Cadoudal, T., Chaoui, K., Dray, C., Monsarrat, B., Schiltz, O., Wang, Y. Y., Couderc, B., Valet, P., Malavaud, B., … Muller, C. (2016). Periprostatic adipocytes act as a driving force for prostate cancer progression in obesity. Nature Communications, 7, 10230. https://doi.org/10.1038/ncomms10230
- Leapman, M. S., Cowan, J. E., Simko, J., Roberge, G., Stohr, B. A., Carroll, P. R., & Cooperberg, M. R. (2017). Application of a prognostic Gleason grade grouping system to assess distant prostate cancer outcomes. European Urology, 71(5), 750–759. https://doi.org/10.1016/j.eururo.2016.11.032
- Lee, Y. J., Kim, D. H., Lee, S. H., Nam, H. S., Roh, M. R., & Cho, M. K. (2010). Chemokine receptor CCR3 expression in malignant cutaneous tumors. Ann Dermatol, 22(4), 412–417. https://doi.org/10.5021/ad.2010.22.4.412
- Markwick, L. J., Clements, D., Roberts, M. E., Ceresa, C. C., Knox, A. J., & Johnson, S. R. (2012). CCR3 induced-p42/44 MAPK activation protects against staurosporine induced-DNA fragmentation but not apoptosis in airway smooth muscle cells. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology, 42(7), 1040–1050. https://doi.org/10.1111/j.1365-2222.2012.04019.x
- Miyagaki, T., Sugaya, M., Murakami, T., Asano, Y., Tada, Y., Kadono, T., Okochi, H., Tamaki, K., & Sato, S. (2011). CCL11-CCR3 interactions promote survival of anaplastic large cell lymphoma cells via ERK1/2 activation. Cancer research, 71(6), 2056–2065. https://doi.org/10.1158/0008-5472.CAN-10-3764
- Mottet, N., Bellmunt, J., Bolla, M., Briers, E., Cumberbatch, M. G., De Santis, M., Fossati, N., Gross, T., Henry, A. M., Joniau, S., Lam, T. B., Mason, M. D., Matveev, V. B., Moldovan, P. C., van den Bergh, R., Van den Broeck, T., van der Poel, H. G., van der Kwast, T. H., Rouvière, O., Schoots, I. G., … Cornford, P. (2017). EAU-ESTRO-SIOG Guidelines on prostate cancer. Part 1: Screening, diagnosis, and local treatment with curative intent. European Urology, 71(4), 618–629. https://doi.org/10.1016/j.eururo.2016.08.003
- Munjal, A., & Leslie, S. W. (2021). Gleason Score. In StatPearls. StatPearls Publishing.
Reddy, K. B., Nabha, S. M., & Atanaskova, N. (2003). Role of MAP kinase in tumor progression and invasion. Cancer Metastasis Reviews, 22(4), 395–403. https://doi.org/10.1023/a:1023781114568
- Tian, M., Chen, L., Ma, L., Wang, D., Shao, B., Wu, J., Wu, H., & Jin, Y. (2016). Expression and prognostic significance of CCL11/CCR3 in glioblastoma. Oncotarget, 7(22), 32617–32627. https://doi.org/10.18632/oncotarget.8958
- Xu, J., Yin, Z., Gao, W., Liu, L., Wang, R., Huang, P., Yin, Y., Liu, P., Yu, R., & Shu, Y. (2012). Meta-analysis on the association between nonsteroidal anti-inflammatory drug use and lung cancer risk. Clinical Lung Cancer, 13(1), 44–51. https://doi.org/10.1016/j.cllc.2011.06.009
- Vela, M., Aris, M., Llorente, M., Garcia-Sanz, J. A., & Kremer, L. (2015). Chemokine receptor-specific antibodies in cancer immunotherapy: Achievements and challenges. Frontiers in Immunology, 6, 12. http://doi.org/10.3389/fimmu.2015.00012
- Zhao, H., Wu, L., Yan, G. et al. Inflammation and tumor progression: signaling pathways and targeted intervention. Sig Transduct Target Ther 6, 263 (2021). https://doi.org/10.1038/s41392-021-00658-5
- Zhu, F., Liu P., Li, J., & Zhang, Y. (2014). Eotaxin-1 promotes prostate cancer cell invasion via activation of the CCR3-ERK pathway and upregulation of MMP-3 expression. Oncology Reports, 31(5), 2049–2054. https://doi.org/10.3892/or.2014.3060
Predictive Value of CCR3 Expression on Diagnosis and Prognostic Classification of the Prostate Adenocarcinoma
Yıl 2022,
Cilt: 11 Sayı: 3, 440 - 446, 04.10.2022
Ayla Solmaz Avcıkurt
,
Eren Altun
,
Fatma Bahar Sunay
Öz
Objective: Chemokines are factors secreted from damaged or infected tissues to induce an inflammatory and immunological reaction. Both chemokines and their receptors are considered as critical actors of tumor formation. Our study aims to investigate CCR-3 expression, which is a chemokine receptor that has recently been found to be secreted by most cancer cells, in prostatic adenocarcinoma (PCa), and reveal any possible relation between the Gleason prognostic grade and CCR-3 levels. Material Method: The study included 25 patients with PCa who underwent prostatectomy, and 25 patients with benign prostate hyperplasia (BPH). CCR-3 was detected at mRNA level by the Real-Time PCR, and at protein level by immunohistochemical (IHC) staining in both PCa and BPH patients. Results from PCa and BPH groups were compared. In PCa group, any correlation between the CCR-3 expression and Gleason prognostic grade was also searched. Results: Although CCR-3 mRNA levels in PCa group were found to be significantly higher than the BPH group (p=0.001), the difference was not significant at the protein level (p=0.205). The difference between the CCR3 expression levels of patients with different Gleason prognostic grades was not significant at both mRNA and protein levels. A statistically significant positive correlation was found between the CCR-3 IHC staining and total PSA levels (p=0.001) in PCa patients. Conclusion: We concluded that the CCR-3 mRNA levels may be useful in the diagnosis of PCa.
Destekleyen Kurum
Balıkesir University
Proje Numarası
BAP. 2017/201
Kaynakça
- Alizadeh, A. M., Shiri, S., Farsinejad, S. (2014). Metastasis review: from bench to bedside. Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine, 35(9), 8483-8523. https://doi.org/10.1007/s13277-014-2421-z
- Andalib, A., Doulabi, H., Maracy, M. R., Rezaei, A., & Hasheminia, S. J. (2013). CCR3, CCR4, CCR5, and CXCR3 expression in peripheral blood CD4+ lymphocytes in gastric cancer patients. Advanced Biomedical Research, 2, 31. https://doi.org/10.4103/2277-9175.108770
- Araújo, J. M. D., Silva, L. A. S., Felix, F. B., Camargo, E. A., & Grespan, R. (2020). CCR3 antagonist impairs estradiol-induced eosinophil migration to the uterus in ovariectomized mice. Brazilian Journal of Medical and Biological Research, 53(1), Article e8659. http://doi.org/10.1590/1414-431X20198659
- Balkwill, B. (2004). Cancer and the chemokine network. Nature Reviews. Cancer, 4(7), 540–550. https://doi.org/10.1038/nrc1388
- Bostwick, D.G., Burke, H.B., Djakiew, D., Euling, S., Ho, S., Landolph, J., Morrison, H., Sonawane, B., Shifflett, T., Waters, D. J., & Timmset, B. (2004). Human prostate cancer risk factors. Cancer, 101(10 Suppl), 2371–2490. https://doi.org/10.1002/cncr.20408
- Castillejos-Molina, R. A., & Gabilondo-Navarro, F. B. (2016). Prostate cancer. Salud publica de Mexico, 58(2), 279–284. https://doi.org/10.21149/spm.v58i2.7797
- Coussens, L. M., & Werb, Z. (2002). Inflammation and cancer. Nature, 420(6917), 860–867. https://doi.org/10.1038/nature01322
- Cuzick, J., Thorat, M. A., Andriole, G., Brawley, O. W., Brown, P. H., Culig, Z., Eeles, R. A., Ford, L. G., Hamdy, F. C., Holmberg, L., Ilic, D., Key, T. J., La Vecchia, C., Lilja, H., Marberger, M., Meyskens, F. L., Minasian, L. M., Parker, C., Parnes, H. L., Perner, S., … Wolk, A. (2014). Prevention and early detection of prostate cancer. The Lancet. Oncology, 15(11), e484–e492. https://doi.org/10.1016/S1470-2045(14)70211-6
- Demirel, C. & Kılçıksız S. (2011). Asetil salisilik asitin radyokoruyucu etkisi. Türk Onkoloji Dergisi, 26(1), 45–53. http://doi.org/10.5505/tjoncol.2011.546
- Epstein, J. I., Egevad, L., Amin, M. B., Delahunt, B., Srigley, J. R., Humphrey, P. A., & Grading Committee (2016a). The 2014 International Society of Urological Pathology (ISUP) consensus conference on Gleason grading of prostatic carcinoma: Definition of grading patterns and proposal for a new grading system. The American Journal of Surgical Pathology, 40(2), 244–252. https://doi.org/10.1097/PAS.0000000000000530
- Epstein, J. I., Zelefsky, M. J., Sjoberg, D. D., Nelson, J. B., Egevad, L., Magi-Galluzzi, C., Vickers, A. J., Parwani, A. V., Reuter, V. E., Fine, S. W., Eastham, J. A., Wiklund, P., Han, M., Reddy, C. A., Ciezki, J. P., Nyberg, T., & Klein, E. A. (2016b). A contemporary prostate cancer grading system: A validated alternative to the Gleason score. European Urology, 69(3), 428–435. https://doi.org/10.1016/j.eururo.2015.06.046
- Guan, X. (2015). Cancer metastases: challenges and opportunities. Acta Pharmaceutica Sinica B, 5(5), 402–418. https://doi.org/10.1016/j.apsb.2015.07.005
- Kleinhans, M., Tun-Kyi, A., Gilliet, M., Kadin, M. E., Dummer, R., Burg, G., & Nestle, F. O. (2003). Functional expression of the eotaxin receptor CCR3 in CD30+ cutaneous T-cell lymphoma. Blood, 101(4), 1487–1493. https://doi.org/10.1182/blood-2002-02-0475
- Kumar, V., Abbas A. K., & Aster, J. C. (2014). Robbins Basic Pathology (9th ed. ). W. B. Saunders Company.
Legler, D. F., & Thelen, M. (2018). New insights in chemokine signaling. F1000Research, 7, 95. https://doi.org/10.12688/f1000research.13130.1
- Laurent, V., Guérard, A., Mazerolles, C., Le Gonidec, S., Toulet, A., Nieto, L., Zaidi, F., Majed, B., Garandeau, D., Socrier, Y., Golzio, M., Cadoudal, T., Chaoui, K., Dray, C., Monsarrat, B., Schiltz, O., Wang, Y. Y., Couderc, B., Valet, P., Malavaud, B., … Muller, C. (2016). Periprostatic adipocytes act as a driving force for prostate cancer progression in obesity. Nature Communications, 7, 10230. https://doi.org/10.1038/ncomms10230
- Leapman, M. S., Cowan, J. E., Simko, J., Roberge, G., Stohr, B. A., Carroll, P. R., & Cooperberg, M. R. (2017). Application of a prognostic Gleason grade grouping system to assess distant prostate cancer outcomes. European Urology, 71(5), 750–759. https://doi.org/10.1016/j.eururo.2016.11.032
- Lee, Y. J., Kim, D. H., Lee, S. H., Nam, H. S., Roh, M. R., & Cho, M. K. (2010). Chemokine receptor CCR3 expression in malignant cutaneous tumors. Ann Dermatol, 22(4), 412–417. https://doi.org/10.5021/ad.2010.22.4.412
- Markwick, L. J., Clements, D., Roberts, M. E., Ceresa, C. C., Knox, A. J., & Johnson, S. R. (2012). CCR3 induced-p42/44 MAPK activation protects against staurosporine induced-DNA fragmentation but not apoptosis in airway smooth muscle cells. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology, 42(7), 1040–1050. https://doi.org/10.1111/j.1365-2222.2012.04019.x
- Miyagaki, T., Sugaya, M., Murakami, T., Asano, Y., Tada, Y., Kadono, T., Okochi, H., Tamaki, K., & Sato, S. (2011). CCL11-CCR3 interactions promote survival of anaplastic large cell lymphoma cells via ERK1/2 activation. Cancer research, 71(6), 2056–2065. https://doi.org/10.1158/0008-5472.CAN-10-3764
- Mottet, N., Bellmunt, J., Bolla, M., Briers, E., Cumberbatch, M. G., De Santis, M., Fossati, N., Gross, T., Henry, A. M., Joniau, S., Lam, T. B., Mason, M. D., Matveev, V. B., Moldovan, P. C., van den Bergh, R., Van den Broeck, T., van der Poel, H. G., van der Kwast, T. H., Rouvière, O., Schoots, I. G., … Cornford, P. (2017). EAU-ESTRO-SIOG Guidelines on prostate cancer. Part 1: Screening, diagnosis, and local treatment with curative intent. European Urology, 71(4), 618–629. https://doi.org/10.1016/j.eururo.2016.08.003
- Munjal, A., & Leslie, S. W. (2021). Gleason Score. In StatPearls. StatPearls Publishing.
Reddy, K. B., Nabha, S. M., & Atanaskova, N. (2003). Role of MAP kinase in tumor progression and invasion. Cancer Metastasis Reviews, 22(4), 395–403. https://doi.org/10.1023/a:1023781114568
- Tian, M., Chen, L., Ma, L., Wang, D., Shao, B., Wu, J., Wu, H., & Jin, Y. (2016). Expression and prognostic significance of CCL11/CCR3 in glioblastoma. Oncotarget, 7(22), 32617–32627. https://doi.org/10.18632/oncotarget.8958
- Xu, J., Yin, Z., Gao, W., Liu, L., Wang, R., Huang, P., Yin, Y., Liu, P., Yu, R., & Shu, Y. (2012). Meta-analysis on the association between nonsteroidal anti-inflammatory drug use and lung cancer risk. Clinical Lung Cancer, 13(1), 44–51. https://doi.org/10.1016/j.cllc.2011.06.009
- Vela, M., Aris, M., Llorente, M., Garcia-Sanz, J. A., & Kremer, L. (2015). Chemokine receptor-specific antibodies in cancer immunotherapy: Achievements and challenges. Frontiers in Immunology, 6, 12. http://doi.org/10.3389/fimmu.2015.00012
- Zhao, H., Wu, L., Yan, G. et al. Inflammation and tumor progression: signaling pathways and targeted intervention. Sig Transduct Target Ther 6, 263 (2021). https://doi.org/10.1038/s41392-021-00658-5
- Zhu, F., Liu P., Li, J., & Zhang, Y. (2014). Eotaxin-1 promotes prostate cancer cell invasion via activation of the CCR3-ERK pathway and upregulation of MMP-3 expression. Oncology Reports, 31(5), 2049–2054. https://doi.org/10.3892/or.2014.3060