J.ophthalmol.(Ukraine).2019;4:69-74.

http://doi.org/10.31288/oftalmolzh201946974

Our current understanding of metastasis and the potential for predicting the course of head and neck squamous cell carcinoma

D.I. Zabolotnyi, Dr Sc (Med), Prof., Acad. of the NAMS of Ukraine;  E.V. Lukach, Dr Sc (Med), Prof.; M.B. Sambur, Dr Sc (Med)

Prof. Kolomiichenko Institute of Otolaryngology, National Academy of Medical Sciences of Ukraine;   Kyiv (Ukraine)

E-mail: erwin@lukach.org

TO CITE THIS ARTICLE: Zabolotnyi DI, Lukach EV, Sambur MB. Our current understanding of metastasis and the potential for predicting the course of head and neck squamous cell carcinoma. J.ophthalmol.(Ukraine).2019;4:69-74. http://doi.org/10.31288/oftalmolzh201946974

 

This review presents recent studies on the mechanisms of malignant neoplasm metastases, particularly, in head and neck squamous cell carcinoma (HNSCC). The involvement of circulating tumor cells (CTC) and cancer stem cells (CSC), and the role of epithelial-to-mesenchymal transition (EMT) and the reverse process, mesenchymal-to-epithelial transition (MET), in the establishment of metastases were noted. The major features of the EMT program are loss of E-cadherin-dependent intercellular adhesion of epithelial cells and increase in tumor cell motility and capacity for migration to and invasion of adjacent tissues and remote organs. Identifying the humoral and cell factors of epithelial cell  microenvironment which induce and regulate the capacity of these cells for malignant transformation is important not only for understanding the mechanisms of oncogenesis, but also for considering whether it is possible to use them as predictive markers or therapeutic targets, which is important for clinical practice.

The review provides data on the role of CTC in the course of HNSCC. It has been demonstrated that the presence of CTCs in patient blood correlated with a higher clinical stage of the disease, thereby evidencing the significant prognostic value of CTC blood levels in head and neck cancer patients and that the presence of CTCs could be used as a monitoring tool for tumor status of head and neck cancer, especially for the early detection of the tumor recurrence and progression, advanced disease and metastases, and assistance in therapeutic effect assessment.

A current approach to identifying the character of and predicting the clinical course of malignant neoplasms is based on the use of the lymph node ratio (LNR) defined as the number of positive lymph nodes divided by the total number of lymph nodes excised. Numerous studies demonstrated that the LNR has a predictive value in head and neck squamous cell carcinoma, may be used as an additional prognostic parameter in combination with the revised TNM classification in HNSCC to predict the course of disease, select adjuvant therapy and control therapy efficacy.

Keywords: head and neck squamous cell carcinoma, metastasis, circulating tumor cells, cancer stem cells, lymph node ratio (LNR)

References

1.Puram S, Tirosh I, Parikh A, Patel A, Yizhak K, Gillespie S, et al. Single-Cell Transcriptomic Analysis of Primary and Metastatic Tumor Ecosystems in Head and Neck Cancer. Cell. 2017 Dec 14;171(7):1611-1624.e24. doi: 10.1016/j.cell.2017.10.044. 

2.Kolesnik OO, editor. [Cancer in Ukraine, 2016-2017. Incidence, mortality, indicators of the oncology service activity. Bulletin of the National Cancer Register]. Kyiv, 2018. Ukrainian.

3.Brovkina AF. [Diseases of the orbit]. Moscow: Meditsina; 1993. Russian.

4.Nassar D, Blanpain C. Cancer Stem Cells: Basic Concepts and Therapeutic Implications. Annu Rev Pathol. 2016 May 23;11:47-76. doi: 10.1146/annurev-pathol-012615-044438.

5.Meacham C, Morrison S. Tumour heterogeneity and cancer cell plasticity. Nature. 2013 Sep 19;501(7467):328-37. doi: 10.1038/nature12624.

6.Kreso A, Dick J. Evolution of the Cancer Stem Cell Model. Cell Stem Cell. 2014 Mar 6;14(3):275-91. doi: 10.1016/j.stem.2014.02.006.

7.Lisianyi M, Grinevich Iu. [The role of stem cells in carcinogenesis and tumor immunotherapy]. Klinicheskaia Onkologiia. 2017;25(1):65–72. Russian.

8.Zheng X, Carstens J, Kim J, Scheible M, Kaye J, Sugimoto H, et al. Epithelial-to-mesenchymal transition is dispensable for metastasis but induces chemoresistance in pancreatic cancer. Nature. 2015 Nov 26;527(7579):525-530. doi: 10.1038/nature16064. 

9.Fischer K, Durrans A, Lee S, Sheng J, Li F, Wong S, et al. Epithelial-to-mesenchymal transition is not required for lung metastasis but contributes to chemoresistance. Nature. 2015 Nov 26;527(7579):472-6. doi: 10.1038/nature15748. Epub 2015 Nov 11.

10.Grinevich Iu. [Ways of development of immunotherapy in oncology. Review of studies performed at the National Cancer Institute].  Klinicheskaia Onkologiia. 2016;21(1):76–80. Russian.

11.Han J, Fujisawa T, Husain SR, Puri RK. Identification and characterization of cancer stem cells in human head and neck squamous cell carcinoma. BMC Cancer. 2014 Mar 11;14:173. doi: 10.1186/1471-2407-14-173.

12.Kim H, Chen Y, Nör F, Warner K, Andrews A, Wagner V, et al. Endothelial-derived interleukin-6 induces cancer stem cell motility by generating a chemotactic gradient towards blood vessels. Oncotarget.  2017 Nov 1;8(59):100339-100352. doi: 10.18632/oncotarget.22225. 

13.Kudriavets IuJ, Bezdenezhnykh NO, Semesiuk NI, Zhilchuk AV, Likhova OO, Kovaliova OA, et al. [Microenvironment of tumor cells as a source of modifiers of epithelial-mesenchymal transition and target for personalized anticancer therapy]. Oncologiia. 2016;18(4), 269-76. Ukrainian.

14.Nieto MA, Huang RY, Jackson RA, Thiery JP. EMT: 2016. Cell.  2016 Jun 30;166(1):21-45. doi: 10.1016/j.cell.2016.06.028.

15.Jolly M, Ware K, Gilja S, Somarelli J, Levine H. EMT and MET: necessary or permissive for metastasis? Mol Oncol. 2017 Jul;11(7):755-769. doi: 10.1002/1878-0261.12083.

16.Gall T, Frampton AE. Gene of the month: E-cadherin (CDH1). J Clin Pathol. 2013 Nov;66(11):928-32. doi: 10.1136/jclinpath-2013-201768.

17.Beerling E, Seinstra D, de Wit E, Kester L, van der Velden D, Maynard C, et al. Plasticity between Epithelial and Mesenchymal States Unlinks EMT from Metastasis-Enhancing Stem Cell Capacity. Cell Rep. 2016 Mar 15;14(10):2281-8. doi: 10.1016/j.celrep.2016.02.034. 

18.Tsubakihara Y, Moustakas A.. Epithelial-Mesenchymal Transition and Metastasis under the Control of Transforming Growth Factor β. Int J Mol Sci. 2018 Nov 20;19(11). pii: E3672. doi: 10.3390/ijms19113672.

19.Derynck R, Muthusamy BP, Saeteurn KY. Signaling pathway cooperation in TGF-β-induced epithelial–mesenchymal transition. Curr Opin Cell Biol. 2014;31:56–66. doi: 10.1016/j.ceb.2014.09.001.

20.Yeung KT, Yang J. Epithelial-mesenchymal transition in tumor metastasis. Mol Oncol. 2017 Jan;11(1):28-39. doi: 10.1002/1878-0261.12017.

21.Tran HD, Luitel K, Kim M, Zhang K, Longmore GD, Tran DD. Transient SNAIL1 Expression Is Necessary for Metastatic Competence in Breast Cancer. Cancer Res. 2014 Nov 1;74(21):6330-40. doi: 10.1158/0008-5472.CAN-14-0923.

22.Ye X, Tam W, Shibue T, Kaygusuz Y, Reinhardt F, Ng Eaton E, Weinberg RA. Distinct EMT programs control normal mammary stem cells and tumour-initiating cells. Nature. 2015 Sep 10;525(7568):256-60. doi: 10.1038/nature14897.

23.Satelli A, Mitra A, Brownlee Z, Xia X, Bellister S, Overman M, et al. Epithelial-mesenchymal transitioned circulating tumor cells capture for detecting tumor progression. Clin Cancer Res. 2015 Feb 15;21(4):899-906. doi: 10.1158/1078-0432.CCR-14-0894.

24.Yu M, Bardia A, Wittner BS, Stott SL, Smas ME, Ting DT, et al. Circulating Breast Tumor Cells Exhibit Dynamic Changes in Epithelial and Mesenchymal Composition. Science.  2013 Feb 1;339(6119):580-4. doi: 10.1126/science.1228522.

25.Santamaria PG, Moreno-Bueno G, Portillo F, Cano A. EMT: Present and future in clinical oncology. Molecular Oncology. Mol Oncol. 2017 Jul;11(7):718-738. doi: 10.1002/1878-0261.12091.

26.Saitoh M. Involvement of partial EMT in cancer progression. J Biochem. 2018 Oct 1;164(4):257-264. doi: 10.1093/jb/mvy047.

27.Brabletz T, Kalluri R, Nieto MA, Weinberg RA. EMT in cancer. Nat Rev Cancer. 2018 Feb;18(2):128-134. doi: 10.1038/nrc.2017.118.

28.Massagué J, Obenauf AC. Metastatic colonization by circulating tumour cells. Nature. 2016 Jan 21;529(7586):298-306. doi: 10.1038/nature17038.

29.Lin M, Chen J, Lu YT, Zhang Y, Song J, Hou S, et al. Nanostructure Embedded Microchips for Detection, Isolation, and Characterization of Circulating Tumor Cells. Acc Chem Res. 2014 Oct 21;47(10):2941-50. doi: 10.1021/ar5001617.

30.Zhang H, Gong S, Liu Y, Liang L, He S,  Zhang Q, et al. [The significance of circulating tumor cells in head and neck squamous cell carcinoma: a preliminary study]. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2018 Jan 7;53(1):39-44. doi: 10.3760/cma.j.issn.1673-0860.2018.01.008.

31.Sun T, Zou K, Yuan Z, Yang C, Lin X, Xiong B. Clinicopathological and prognostic significance of circulating tumor cells in patients with head and neck cancer: a meta-analysis. Oncotargets Ther. 2017 Aug 4;10:3907-3916. doi: 10.2147/OTT.S136530. 

32.Lou J, Guo L, Zheng WH, Zhao J, Zhao JQ, Liang Z. [Peripheral blood circulating tumor cells in local advanced head and neck squamous cell carcinoma]. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2017 Nov 7;52(11):824-829. doi: 10.3760/cma.j.issn.1673-0860.2017.11.005.

33.Sano D, Yabuki K, Takahashi H, Arai Y, Chiba Y, Tanabe T, et al. Lymph node ratio as a prognostic factor for survival in patients with head and neck squamous cell carcinoma. Auris Nasus Larynx. 2018 Aug;45(4):846-853. doi: 10.1016/j.anl.2017.11.015.

34.Jacobi C, Rauch J, Hagemann J, Lautz T, Reiter M, Baumeister P. Prognostic value of the lymph node ratio in oropharyngeal carcinoma stratified for HPV-status. Eur Arch Otorhinolaryngol. 2018 Feb;275(2):515-524. doi: 10.1007/s00405-017-4833-z.

35.Reinisch S, Kruse A, Bredell M, Lübbers HT, Gander T, Lanzer M. Is Lymph-node Ratio a Superior Predictor than Lymph Node Status for Recurrence-free and Overall Survival in Patients with Head and Neck Squamous Cell Carcinoma? Ann Surg Oncol. 2014 Jun;21(6):1912-8. doi: 10.1245/s10434-014-3634-5.

36.Boumahdi S, Driessens G, Lapouge G, Rorive S, Nassar D, Le Mercier M, et al. SOX2 controls tumour initiation and cancer stem-cell functions in squamous-cell carcinoma. Nature. 2014 Jul 10;511(7508):246-50. doi: 10.1038/nature13305.

37.Tan TZ, Miow QH, Miki Y, Noda T, Mori S, Huang RY, Thiery JP. Epithelial-mesenchymal transition spectrum quantification and its efficacy in deciphering survival and drug responses of cancer patients. EMBO Mol Med. 2014 Oct;6(10):1279-93. doi: 10.15252/emmm.201404208.

38.Marcucci F, Stassi G, De Maria R. Epithelial–mesenchymal transition: a new target in anticancer drug discovery. Nat Rev Drug Discov. 2016 May;15(5):311-25. doi: 10.1038/nrd.2015.13.

39.Pastushenko I, Brisebarre A, Sifrim A, Fioramonti M, Revenco T, Boumahdi S, et al. Identification of the tumour transition states occurring during EMT. Nature. 2018 Apr;556(7702):463-468. doi: 10.1038/s41586-018-0040-3.

The authors certify that they have no conflicts of interest in the subject matter or materials discussed in this manuscript.