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Tumor Biology

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20.01.2016 | Original Article

B7-H3 increases thymidylate synthase expression via the PI3k-Akt pathway

verfasst von: Bo Jiang, Fen Liu, ZhiHui Liu, Ting Zhang, Dong Hua

Erschienen in: Tumor Biology | Ausgabe 7/2016

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Abstract

B7-H3, a member of the B7 family, has been reported to be highly expressed in colorectal cancer and is associated with poor prognosis and overall survival. In this study, we found that overexpression of B7-H3 protected SW80 and HCT8 cells from 5-fluorouracil (5-FU) using CCK-8 assays by inducing resistance to 5-FU chemotherapy. Further investigation has revealed elevated expression of thymidylate synthase (TS) and upregulation of the PI3-kinase (PI3K)/Akt pathway in B7-H3 overexpressing cells. The effects of B7-H3 on activation of the PI3K/Akt pathway and elevation of TS expression could be blocked by LY294002, a specific inhibitor of the PI3K signaling pathway. These results implied that B7-H3 can induce colorectal cancer cell resistance to 5-FU by increasing TS expression and PI3K/Akt/TS signaling and plays an important role during these processes. This study provides more proof concerning the non-immunology effect of B7 molecules, a reminder that both co-stimulatory or inhibitory effects and non-immunology effects should be devoted equal attention.

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Robert C, Ribas A, Wolchok JD, Hodi FS, Hamid O, Kefford R, et al. Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial. Lancet. 2014;384:1109–17.CrossRefPubMed

Ribas AWJD, Robert C. Updated clinical efficacy of the anti-pd-1 monoclonal antibody pembrolizumab (pembro, mk-3475) in 411 patients (pts) with melanoma (mel). Pigment Cell Melanoma Res. 2014;27:1222.

D’Angelo S.P. LJ, Weber J: Smr; 2014. Efficacy and safety of nivolumab vs investigator’s choice chemotherapy (icc) in subgroups of patients with advanced melanoma after prior anti-ctla-4 therapy. (Abstract LBA)

Robert C, Long GV, Brady B, Dutriaux C, Maio M, Mortier L, et al. Nivolumab in previously untreated melanoma without braf mutation. N Engl J Med. 2015;372:320–30.CrossRefPubMed

Tsai KK, Daud AI. The role of anti-pd-1/pd-l1 agents in melanoma: progress to date. Drugs. 2015;75:563–75.CrossRefPubMed

Ramalingam S.S. MJ, Planchard D. Presented at: 2014 multidisciplinary symposium in thoracic oncology; October 30–November 1; Chicago, IL. 2014. Phase ii study of nivolumab (anti-pd-1, bms-936558, ono-4538) in patients with advanced, refractory squamous non-small cell lung cancer. (Abstract Number: LB2)

Powles T, Eder JP, Fine GD, Braiteh FS, Loriot Y, Cruz C, et al. Mpdl3280a (anti-pd-l1) treatment leads to clinical activity in metastatic bladder cancer. Nature. 2014;515:558–62.CrossRefPubMed

Nanda R. CLQ, Dees E.C., Berger R., Gupta S., Geva R. S.: Antonio breast cancer symposium, December 9–13, 2014. KEYNOTE 2014;012: triple negative breast cancer.

Ascierto PA, Marincola FM. The year of anti-pd-1/pd-l1s against melanoma and beyond. EBioMedicine. 2015;2:92–3.CrossRefPubMedPubMedCentral

10.

Sun M, Richards S, Prasad DV, Mai XM, Rudensky A, Dong C. Characterization of mouse and human b7-h3 genes. J Immunol. 2002;168:6294–7.CrossRefPubMed

11.

Hu Y, Lv X, Wu Y, Xu J, Wang L, Chen W, et al. Expression of costimulatory molecule b7-h3 and its prognostic implications in human acute leukemia. Hematology. 2015;20:187–95.CrossRefPubMed

12.

Baral A, Ye HX, Jiang PC, Yao Y, Mao Y. B7-h3 and b7-h1 expression in cerebral spinal fluid and tumor tissue correlates with the malignancy grade of glioma patients. Oncology letters. 2014;8:1195–201.PubMedPubMedCentral

13.

Wang F, Wang G, Liu T, Yu G, Zhang G, Luan X. B7-h3 was highly expressed in human primary hepatocellular carcinoma and promoted tumor progression. Cancer Investig. 2014;32:262–71.CrossRef

14.

Sun J, Mao Y, Zhang YQ, Guo YD, Mu CY, Fu FQ, et al. Clinical significance of the induction of macrophage differentiation by the costimulatory molecule b7-h3 in human non-small cell lung cancer. Oncology letters. 2013;6:1253–60.PubMedPubMedCentral

15.

Maeda N, Yoshimura K, Yamamoto S, Kuramasu A, Inoue M, Suzuki N, et al. Expression of b7-h3, a potential factor of tumor immune evasion in combination with the number of regulatory t cells, affects against recurrence-free survival in breast cancer patients. Ann Surg Oncol. 2014;21 Suppl 4:S546–54.CrossRefPubMed

16.

Chavin G, Sheinin Y, Crispen PL, Boorjian SA, Roth TJ, Rangel L, et al. Expression of immunosuppresive b7-h3 ligand by hormone-treated prostate cancer tumors and metastases. Clin Cancer Res. 2009;15:2174–80.CrossRefPubMedPubMedCentral

17.

Roth TJ, Sheinin Y, Lohse CM, Kuntz SM, Frigola X, Inman BA, et al. B7-h3 ligand expression by prostate cancer: A novel marker of prognosis and potential target for therapy. Cancer Res. 2007;67:7893–900.CrossRefPubMed

18.

Wang J, Chong KK, Nakamura Y, Nguyen L, Huang SK, Kuo C, et al. B7-h3 associated with tumor progression and epigenetic regulatory activity in cutaneous melanoma. J Invest Dermatol. 2013;133:2050–8.CrossRefPubMedPubMedCentral

19.

Zhao X, Li DC, Zhu XG, Gan WJ, Li Z, Xiong F, et al. B7-h3 overexpression in pancreatic cancer promotes tumor progression. Int J Mol Med. 2013;31:283–91.PubMed

20.

Siegel R, Desantis C, Jemal A. Colorectal cancer statistics, 2014. CA Cancer J Clin. 2014;64:104–17.CrossRefPubMed

21.

Ingebrigtsen VA, Boye K, Nesland JM, Nesbakken A, Flatmark K, Fodstad O. B7-h3 expression in colorectal cancer: associations with clinicopathological parameters and patient outcome. BMC Cancer. 2014;14:602.CrossRefPubMedPubMedCentral

22.

Bin Z, Guangbo Z, Yan G, Huan Z, Desheng L, Xueguang Z. Overexpression of b7-h3 in cd133+ colorectal cancer cells is associated with cancer progression and survival in human patients. J Surg Res. 2014;188:396–403.CrossRefPubMed

23.

Ingebrigtsen VA, Boye K, Tekle C, Nesland JM, Flatmark K, Fodstad O. B7-h3 expression in colorectal cancer: nuclear localization strongly predicts poor outcome in colon cancer. Int J Cancer Journal international du cancer. 2012;131:2528–36.CrossRefPubMed

24.

Zhang T, Jiang B, Zou ST, Liu F, Hua D. Overexpression of b7-h3 augments anti-apoptosis of colorectal cancer cells by jak2-stat3. World J Gastroenterol. 2015;21:1804–13.CrossRefPubMedPubMedCentral

25.

Liu F, Zhang T, Zou S, Jiang B, Hua D. B7h3 promotes cell migration and invasion through the jak2/stat3/mmp9 signaling pathway in colorectal cancer. Mol Med Rep. 2015.

26.

Zang X, Allison JP. The b7 family and cancer therapy: costimulation and coinhibition. Clin Cancer Res. 2007;13:5271–9.CrossRefPubMed

27.

Fukushima M, Morita M, Ikeda K, Nagayama S. Population study of expression of thymidylate synthase and dihydropyrimidine dehydrogenase in patients with solid tumors. Int J Mol Med. 2003;12:839–44.PubMed

28.

Diasio RB, Johnson MR. The role of pharmacogenetics and pharmacogenomics in cancer chemotherapy with 5-fluorouracil. Pharmacology. 2000;61:199–203.CrossRefPubMed

29.

Silvestris N, Marech I, Brunetti AE, Azzariti A, Numico G, Cicero G, et al. Predictive factors to targeted treatment in gastrointestinal carcinomas. Cancer Biomark. 2014;14:151–62.CrossRefPubMed

30.

Wang L, Wang R, Pan Y, Sun Y, Zhang J, Chen H. The pemetrexed-containing treatments in the non-small cell lung cancer is -/low thymidylate synthase expression better than +/high thymidylate synthase expression: a meta-analysis. BMC Cancer. 2014;14:205.CrossRefPubMedPubMedCentral

31.

Arima S, Tachikawa D, Kawahara K, Futami K. Thymidylate synthase activity after preoperative administration of 5-fu in patients with gastric or colorectal cancer. Gan to kagaku ryoho Cancer & chemotherapy. 2000;27:703–10.

32.

Ishida H, Shirakawa K, Ohsawa T, Sobajima J, Hayashi Y, Nakada H, et al. Expression of mrna levels of thymidylate synthase, dihydropyrimidine dehydrogenase, and orotate phosphoribosyltransferase of colorectal cancer--relationships among mrna levels in association with response to 5-fu based treatment. Gan to kagaku ryoho Cancer & chemotherapy. 2005;32:1929–34.

33.

Kamoshida S, Matsuoka H, Ishikawa T, Maeda K, Shimomura R, Inada K, et al. Immunohistochemical evaluation of thymidylate synthase (ts) and p16ink4a in advanced colorectal cancer: implication of ts expression in 5-fu-based adjuvant chemotherapy. Jpn J Clin Oncol. 2004;34:594–601.CrossRefPubMed

34.

Kim SH, Kwon HC, Oh SY, Lee DM, Lee S, Lee JH, et al. Prognostic value of ercc1, thymidylate synthase, and glutathione s-transferase pi for 5-fu/oxaliplatin chemotherapy in advanced colorectal cancer. Am J Clin Oncol. 2009;32:38–43.CrossRefPubMed

35.

Subbarayan PR, Sarkar M, Nelson G, Benitez E, Singhal S, Ardalan B. Chronic exposure of colorectal cancer cells in culture to fluoropyrimidine analogs induces thymidylate synthase and suppresses p53. A molecular explanation for the mechanism of 5-fu resistance. Anticancer Res. 2010;30:1149–56.PubMed

36.

Tsujimoto H, Tsukioka S, Ono S, Sakamoto E, Sakamoto K, Tsuta K, et al. Effect of leucovorin on the antitumor efficacy of the 5-fu prodrug, tegafur-uracil, in human colorectal cancer xenografts with various expression levels of thymidylate synthase. Oncol Lett. 2010;1:973–80.PubMedPubMedCentral

37.

Tanaka-Nozaki M, Tajiri T, Tanaka N, Furukawa K, Takasaki H, Yoshimura K, et al. Intratumoral induction of thymidylate synthase mrna by 5-fu in colorectal cancer patients: association with survival. Oncol Rep. 2003;10:1425–9.PubMed

38.

Raymond E, Louvet C, Tournigand C, Coudray AM, Faivre S, De Gramont A, et al. Pemetrexed disodium combined with oxaliplatin, sn38, or 5-fluorouracil, based on the quantitation of drug interactions in human ht29 colon cancer cells. Int J Oncol. 2002;21:361–7.PubMed

39.

Bischof M, Huber P, Stoffregen C, Wannenmacher M, Weber KJ. Radiosensitization by pemetrexed of human colon carcinoma cells in different cell cycle phases. Int J Radiat Oncol Biol Phys. 2003;57:289–92.CrossRefPubMed

40.

Avallone A, Di Gennaro E, Silvestro L, Iaffaioli VR, Budillon A. Targeting thymidylate synthase in colorectal cancer: critical re-evaluation and emerging therapeutic role of raltitrexed. Expert Opin Drug Saf. 2014;13:113–29.CrossRefPubMed

41.

Lee KH, Hur HS, Im SA, Lee J, Kim HP, Yoon YK, et al. Rad001 shows activity against gastric cancer cells and overcomes 5-fu resistance by downregulating thymidylate synthase. Cancer Lett. 2010;299:22–8.CrossRefPubMed

42.

Danielsen SA, Eide PW, Nesbakken A, Guren T, Leithe E, Lothe RA. Portrait of the pi3k/akt pathway in colorectal cancer. Biochim Biophys Acta. 1855;2015:104–21.

43.

Franke TF. Pi3k/akt: getting it right matters. Oncogene. 2008;27:6473–88.CrossRefPubMed

44.

Manning BD, Cantley LC. Akt/pkb signaling: navigating downstream. Cell. 2007;129:1261–74.CrossRefPubMedPubMedCentral

45.

Fulda S. The pi3k/akt/mtor pathway as therapeutic target in neuroblastoma. Curr Cancer Drug Targets. 2009;9:729–37.CrossRefPubMed

46.

Chiarini F, Del Sole M, Mongiorgi S, Gaboardi GC, Cappellini A, Mantovani I, et al. The novel akt inhibitor, perifosine, induces caspase-dependent apoptosis and downregulates p-glycoprotein expression in multidrug-resistant human t-acute leukemia cells by a jnk-dependent mechanism. Leukemia. 2008;22:1106–16.CrossRefPubMed

47.

Fei HR, Chen G, Wang JM, Wang FZ. Perifosine induces cell cycle arrest and apoptosis in human hepatocellular carcinoma cell lines by blockade of akt phosphorylation. Cytotechnology. 2010;62:449–60.CrossRefPubMedPubMedCentral

48.

Chen GQ, Tang CF, Shi XK, Lin CY, Fatima S, Pan XH, Yang DJ, Zhang G, Lu AP, Lin SH, Bian ZX: Halofuginone inhibits colorectal cancer growth through suppression of akt/mtorc1 signaling and glucose metabolism. Oncotarget 2015

49.

Liu G, Song Y, Cui L, Wen Z, Lu X. Inositol hexaphosphate suppresses growth and induces apoptosis in ht-29 colorectal cancer cells in culture: Pi3k/akt pathway as a potential target. Int J Clin Exp Pathol. 2015;8:1402–10.PubMedPubMedCentral

50.

Prabhu VV, Allen JE, Dicker DT, El-Deiry WS. Small-molecule onc201/tic10 targets chemotherapy-resistant colorectal cancer stem-like cells in an akt/foxo3a/trail-dependent manner. Cancer Res. 2015;75:1423–32.CrossRefPubMedPubMedCentral

51.

Qin J, Teng J, Zhu Z, Chen J, Huang WJ: Genistein induces activation of the mitochondrial apoptosis pathway by inhibiting phosphorylation of akt in colorectal cancer cells. Pharmaceutical biology 2015:1-6.

52.

Tang Y, Liu P, Tian Y, Xu Y, Ren F, Cui X, et al. Overexpression of ribonuclease inhibitor defines good prognosis and suppresses proliferation and metastasis in human colorectal cancer cells via pi3k/akt pathway. Clin Transl Oncol. 2015;17:306–13.CrossRefPubMed

53.

Wang F, Ruan XJ, Zhang HY. Bde-99 (2,2′,4,4′,5-pentabromodiphenyl ether) triggers epithelial-mesenchymal transition in colorectal cancer cells via pi3k/akt/snail signaling pathway. Tumori. 2015;101:238–45.CrossRefPubMed

54.

Nagaraju GP, Alese OB, Landry J, Diaz R, El-Rayes BF. Hsp90 inhibition downregulates thymidylate synthase and sensitizes colorectal cancer cell lines to the effect of 5fu-based chemotherapy. Oncotarget. 2014;5:9980–91.CrossRefPubMedPubMedCentral

55.

Kang FB, Wang L, Jia HC, Li D, Li HJ, Zhang YG, et al. B7-h3 promotes aggression and invasion of hepatocellular carcinoma by targeting epithelial-to-mesenchymal transition via jak2/stat3/slug signaling pathway. Cancer Cell Int. 2015;15:45.CrossRefPubMedPubMedCentral

Titel: B7-H3 increases thymidylate synthase expression via the PI3k-Akt pathway
verfasst von: Bo Jiang
Fen Liu
ZhiHui Liu
Ting Zhang
Dong Hua
Publikationsdatum: 20.01.2016
Verlag: Springer Netherlands
Erschienen in: Tumor Biology / Ausgabe 7/2016
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI: https://doi.org/10.1007/s13277-015-4740-0

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B7-H3 increases thymidylate synthase expression via the PI3k-Akt pathway

Abstract

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