An obstructive role of NK cells on metastatic growth of clear‑cell sarcoma cells in a xenoplant murine model

Hanamatsu,Yuki; Saigo,Chiemi; Kito,Yusuke; Takeuchi,Tamotsu

doi:10.3892/mco.2020.2171

An obstructive role of NK cells on metastatic growth of clear‑cell sarcoma cells in a xenoplant murine model

Authors:
- Yuki Hanamatsu
- Chiemi Saigo
- Yusuke Kito
- Tamotsu Takeuchi
View Affiliations

Affiliations: Department of Pathology and Translational Research, Gifu University Graduate School of Medicine, Gifu 501‑1193, Japan
Published online on: November 12, 2020 https://doi.org/10.3892/mco.2020.2171
Article Number: 9
Copyright: © Hanamatsu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Clear cell sarcoma (CCS) affects the deep soft tissues in young adults and is known to have high rates of metastasis, including lymphatic metastasis. In our previous study an xenoplant model of CCS was established, which exhibited local tumor growth, lymphatic metastasis, and distant metastasis in SCID‑Beige mice. In the current study, the role of NK cells during metastasis in the same xenoplant murine model was investigated. Injection of murine or human NK cells significantly suppressed the metastasis of HS‑MM CCS cells in SCID‑Beige mice. Notably, reverse transcription‑quantitative PCR analysis demonstrated that injection of NK cells did not alter the mRNA expression levels of ERSR1‑ATF1, which is specifically transcribed in CCS, in the buffy coat of circulating blood cells of HS‑MM‑xenoplanted SCID‑Beige mice. BALB/c nude mice xenoplanted with HS‑MM cells exhibited local growth without evident metastasis, whereas inoculation with the anti‑asialo‑GM1 antibody, which has previously been found to abolish NK‑cell activity, resulted in metastasis of HS‑MM cells in BALB/c nude mice. The injection of the anti‑CD96 antibody, which increases the cytotoxicity of NK cells, significantly suppressed the metastasis of HS‑MM cells in SCID‑Beige mice. These results indicated that NK cells impaired the metastatic tumor microenvironments in the present mice xenoplant model.

View Figures

View References

1	Zucman J, Delattre O, Desmaze C, Epstein AL, Stenman G, Speleman F, Fletchers CD, Aurias A and Thomas G: EWS and ATF-1 gene fusion induced by t(12;22) translocation in malignant melanoma of soft parts. Nat Genet. 4:341–345. 1993.PubMed/NCBI View Article : Google Scholar
2	Thway K and Fisher C: Tumors with EWSR1-CREB1 and EWSR1-ATF1 fusions: The current status. Am J Surg Pathol. 36:e1–e11. 2012.PubMed/NCBI View Article : Google Scholar
3	Enzinger FM: Clear-cell sarcoma of tendons and aponeuroses. An analysis of 21 cases. Cancer. 18:1163–1174. 1965.PubMed/NCBI View Article : Google Scholar
4	Chung EB and Enzinger FM: Malignant melanoma of soft parts. A reassessment of clear cell sarcoma. Am J Surg Pathol. 7:405–413. 1983.PubMed/NCBI View Article : Google Scholar
5	Ibrahim RM, Steenstrup Jensen S and Juel J: Clear cell sarcoma-A review. J Orthop. 15:963–966. 2018.PubMed/NCBI View Article : Google Scholar
6	Andreou D and Tunn PU: Sentinel node biopsy in soft tissue sarcoma. Recent Results Cancer Res. 179:25–36. 2009.PubMed/NCBI View Article : Google Scholar
7	Andreou D, Boldt H, Werner M, Hamann C, Pink D and Tunn PU: Sentinel node biopsy in soft tissue sarcoma subtypes with a high propensity for regional lymphatic spread-results of a large prospective trial. Ann Oncol. 24:1400–1405. 2013.PubMed/NCBI View Article : Google Scholar
8	Mavrogenis A, Bianchi G, Stavropoulos N, Papagelopoulos P and Ruggieri P: Clinicopathological features, diagnosis and treatment of clear cell sarcoma/melanoma of soft parts. Hippokratia. 17:298–302. 2013.PubMed/NCBI
9	Egawa Y, Saigo C, Kito Y, Moriki T and Takeuchi T: Therapeutic potential of CPI-613 for targeting tumorous mitochondrial energy metabolism and inhibiting autophagy in clear cell sarcoma. PLoS One. 13(e0198940)2018.PubMed/NCBI View Article : Google Scholar
10	Kawashima K, Saigo C, Kito Y, Hanamatsu Y, Egawa Y and Takeuchi T: CD151 confers metastatic potential to clear cell sarcoma of the soft tissue in animal model. Oncol Lett. 17:4811–4818. 2019.PubMed/NCBI View Article : Google Scholar
11	MacDougall JR, Croy BA, Chapeau C and Clark DA: Demonstration of a splenic cytotoxic effector cell in mice of genotype SCID/SCID.BG/BG. Cell Immunol. 130:106–117. 1990.PubMed/NCBI View Article : Google Scholar
12	Budzynski W and Radzikowski C: Cytotoxic cells in immunodeficient athymic mice. Immunopharmacol Immunotoxicol. 16:319–346. 1994.PubMed/NCBI View Article : Google Scholar
13	Sonobe H, Furihata M, Iwata J, Ohtsuki Y, Mizobuchi H, Yamamoto H and Kumano O: Establishment and characterization of a new human clear-cell sarcoma cell-line, HS-MM. J Pathol. 169:317–322. 1993.PubMed/NCBI View Article : Google Scholar
14	Sonobe H, Takeuchi T, Taguchi T, Shimizu K, Iwata J, Furihata M and Ohtsuki Y: Further characterization of the human clear cell sarcoma cell line HS-MM demonstrating a specific t(12;22)(q13;q12) translocation and hybrid EWSR1/ATF-1 transcript. J Pahol. 187:594–597. 1999.PubMed/NCBI View Article : Google Scholar
15	Takeuchi T, Adachi Y and Nagayama T: A WWOX-binding molecule, transmembrane protein 207, is related to the invasiveness of gastric signet-ring cell carcinoma. Carcinogenesis. 33:548–554. 2012.PubMed/NCBI View Article : Google Scholar
16	Asano Y, Takeuchi T, Okubo H, Saigo C, Kito Y, Iwata Y, Futamura M and Yoshida K: Nuclear localization of LDL receptor-related protein 1B in mammary gland carcinogenesis. J Mol Med (Berl). 97:257–268. 2019.PubMed/NCBI View Article : Google Scholar
17	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta C(T)) method. Methods. 25:402–408. 2001.PubMed/NCBI View Article : Google Scholar
18	Kanda Y: Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant. 48:452–458. 2013.PubMed/NCBI View Article : Google Scholar
19	R Core Team: R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, 2014.
20	Chan CJ, Martinet L, Gilfillan S, Souza-Fonseca-Guimaraes F, Chow MT, Town L, Ritchie DS, Colonna M, Andrews DM and Smyth MJ: The receptors CD96 and CD226 oppose each other in the regulation of natural killer cell functions. Nat Immunol. 15:431–438. 2014.PubMed/NCBI View Article : Google Scholar
21	Ochoa MC, Minute L, Rodriguez I, Garasa S, Perez-Ruiz E, Inogés S, Melero I and Berraondo P: Antibody-dependent cell cytotoxicity: Immunotherapy strategies enhancing effector NK cells. Immunol Cell Biol. 95:347–355. 2017.PubMed/NCBI View Article : Google Scholar
22	Faltas B: Cornering metastases: Therapeutic targeting of circulating tumor cells and stem cells. Front Oncol. 2(68)2012.PubMed/NCBI View Article : Google Scholar
23	Narasimhan PB, Eggert T, Zhu YP, Marcovecchio P, Meyer MA, Wu R and Hedrick CC: Patrolling monocytes control NK cell expression of activating and stimulatory receptors to curtail lung metastases. J Immunol. 204:192–198. 2020.PubMed/NCBI View Article : Google Scholar
24	Bi J and Tian Z: NK cell dysfunction and checkpoint immunotherapy. Front Immunol. 10(1999)2019.PubMed/NCBI View Article : Google Scholar
25	López-Soto A, Gonzalez S, Smyth MJ and Galluzzi L: Control of metastasis by NK cells. Cancer Cell. 32:135–154. 2017.PubMed/NCBI View Article : Google Scholar