Abstract

Research Article

A comparative study of single or dual treatment of theranostic 188Re-Liposome on microRNA expressive profiles of orthotopic human head and neck tumor model

Shan-Ying Wang, Liang-Ting Lin, Bing-Ze Lin, Chih-Hsien Chang, Chun-Yuan Chang, Min-Ying Lin and Yi-Jang Lee*

Published: 25 February, 2021 | Volume 5 - Issue 1 | Pages: 001-012

Background: 188Re-liposome has been used for evaluating the theranostic efficacy on human head and neck squamous cell carcinoma (HNSCC) at preclinical stages. Here we furthercompared the microRNA expressive profile in orthtopic HNSCC tumor model exposed to 188Re-liposome.

Methods: A single dose or dual doses of 188Re-liposome was intravenously injected into tumor-bearing mice followed by the Cerenkov luminescent imaging (CLI) for monitoring the accumulation of 188Re-liposome in tumors. The microRNA expressive profile was generated using the Taqman® OpenArray® Human MicroRNA Panel followed by the DIANA mirPath analysis, KEGG signaling pathways prediction, and Kaplan-Meier survival analysis for predicting the prognostic role of 188Re-liposome affected microRNAs.

Results: Dual doses of 188Re-liposome exhibited a better tumor suppression than a single dose of 188Re-liposome, including reduced tumor size, Ki-67 proliferative marker, and epithelial-mesenchymal transition (EMT) related factors. The microRNA expressive profiles showed that 22 microRNAs and 19 microRNAs were up-regulated and down-regulated by dual doses of 188Re-liposome, respectively. Concomitantly, these two groups of microRNAs were inversely regulated by a single dose of 188Re-liposome accordingly. These microRNAs influenced most downstream genes involved in cancer related signaling pathways. Further, miR-520e and miR-522-3p were down-regulated whereas miR-186-5p and miR-543 were up-regulated by dual doses of 188Re-liposome, and they separately affected most of genes involved in their corresponding pathways with high significance. Additionally, high expressions of miR-520e and miR-522-3p were associated with lower survival rate of HNSCC patients.

Conclusion: MicroRNA expression could be used to evaluate the therapeutic efficacy and regarded prognostic factors using different doses of 188Re-liposome.

Read Full Article HTML DOI: 10.29328/journal.hor.1001024 Cite this Article Read Full Article PDF

Keywords:

188Re-liposome; HNSCC; Cerenkov luminescent imaging; microRNA expressive profile; prognostic factors

References

  1. Bodalal Z, Trebeschi S, Nguyen-Kim TDL, Schats W, Beets-Tan R. Radiogenomics: bridging imaging and genomics. Abdom Radiol (NY). 2019; 44: 1960-1984. PubMed: https://pubmed.ncbi.nlm.nih.gov/31049614/
  2. Snyder AR, Morgan WF. Gene expression profiling after irradiation: clues to understanding acute and persistent responses? Cancer Metastasis Rev. 2004; 23: 259-268. PubMed: https://pubmed.ncbi.nlm.nih.gov/15197327/
  3. Yordanova A, Eppard E, Kurpig S, Bundschuh RA, Schonberger S, et al. Theranostics in nuclear medicine practice. Onco Targets Ther. 2017; 10: 4821-4828. PubMed: https://pubmed.ncbi.nlm.nih.gov/29042793/
  4. Lepareur N, Lacoeuille F, Bouvry C, Hindre F, Garcion E, et al. Rhenium-188 Labeled Radiopharmaceuticals: Current Clinical Applications in Oncology and Promising Perspectives. Front Med (Lausanne). 2019; 6: 132. PubMed: https://pubmed.ncbi.nlm.nih.gov/31259173/
  5. Kennedy CM, Pinkerton TC. Technetium carboxylate complexes--I. A review of Tc, Re and Mo carboxylate chemistry. International journal of radiation applications and instrumentation Part A, Applied radiation and isotopes. 1988; 39: 1159-1165.
  6. Deutsch E, Libson K, Vanderheyden JL, Ketring AR, Maxon HR. The chemistry of rhenium and technetium as related to the use of isotopes of these elements in therapeutic and diagnostic nuclear medicine. Int J Rad Appl Instrum B. 1986; 13: 465-477. PubMed: https://pubmed.ncbi.nlm.nih.gov/3793504/
  7. Wang HY, Lin WY, Chen MC, Lin T, Chao CH, et al. Inhibitory effects of Rhenium-188-labeled Herceptin on prostate cancer cell growth: a possible radioimmunotherapy to prostate carcinoma. Int J Radiation Biol. 2013; 89: 346-355.
  8. Chang CH, Liu SY, Chi CW, Yu HL, Chang TJ, et al. External beam radiotherapy synergizes (1)(8)(8)Re-liposome against human esophageal cancer xenograft and modulates (1)(8)(8)Re-liposome pharmacokinetics. Int J Nanomedicine. 2015; 10: 3641-3649. PubMed: https://pubmed.ncbi.nlm.nih.gov/26056445/
  9. Lin LT, Chang CH, Yu HL, Liu RS, Wang HE, et al. Evaluation of the therapeutic and diagnostic effects of PEGylated liposome-embedded 188Re on human non-small cell lung cancer using an orthotopic small-animal model. J Nucl Med. 2014; 55: 1864-1870. PubMed: https://pubmed.ncbi.nlm.nih.gov/25349220/
  10. Huang FY, Lee TW, Chang CH, Chen LC, Hsu WH, et al. Evaluation of 188Re-labeled PEGylated nanoliposome as a radionuclide therapeutic agent in an orthotopic glioma-bearing rat model. Int J Nanomedicine. 2015; 10: 463-473. PubMed: https://pubmed.ncbi.nlm.nih.gov/25624760/
  11. Chang YJ, Chang CH, Yu CY, Chang TJ, Chen LC, et al. Therapeutic efficacy and microSPECT/CT imaging of 188Re-DXR-liposome in a C26 murine colon carcinoma solid tumor model. Nucl Med Biol. 2010; 37: 95-104. PubMed: https://pubmed.ncbi.nlm.nih.gov/20122674/
  12. Lin LT, Chang CY, Chang CH, Wang HE, Chiou SH, et al. Involvement of let-7 microRNA for the therapeutic effects of Rhenium-188-embedded liposomal nanoparticles on orthotopic human head and neck cancer model. Oncotarget. 2016; 7: 65782-6596. PubMed: https://pubmed.ncbi.nlm.nih.gov/27588466/
  13. Goins B, Bao A, Phillips WT. Techniques for loading technetium-99m and rhenium-186/188 radionuclides into pre-formed liposomes for diagnostic imaging and radionuclide therapy. Methods Mol Biol. 2010; 606: 469-491.
  14. Maruyama K. Intracellular targeting delivery of liposomal drugs to solid tumors based on EPR effects. Adv Drug Deliv Rev. 2011; 63: 161-169. PubMed: https://pubmed.ncbi.nlm.nih.gov/20869415/
  15. Chang CY, Chen CC, Lin LT, Chang CH, Chen LC, et al. PEGylated liposome-encapsulated rhenium-188 radiopharmaceutical inhibits proliferation and epithelial-mesenchymal transition of human head and neck cancer cells in vivo with repeated therapy. Cell Death Discov. 2018; 4: 100. PubMed: https://pubmed.ncbi.nlm.nih.gov/30393570/
  16. Zheng HC. The molecular mechanisms of chemoresistance in cancers. Oncotarget. 2017; 8: 59950-59964. PubMed: https://pubmed.ncbi.nlm.nih.gov/28938696/
  17. Chang YJ, Chang CH, Chang TJ, Yu CY, Chen LC, et al. Biodistribution, pharmacokinetics and microSPECT/CT imaging of 188Re-bMEDA-liposome in a C26 murine colon carcinoma solid tumor animal model. Anticancer Res. 2007; 27: 2217-2225. PubMed: https://pubmed.ncbi.nlm.nih.gov/17695506/
  18. Tuominen VJ, Ruotoistenmaki S, Viitanen A, Jumppanen M, Isola J. ImmunoRatio: a publicly available web application for quantitative image analysis of estrogen receptor (ER), progesterone receptor (PR), and Ki-67. Breast Cancer Res. 2010; 12: R56. PubMed: https://pubmed.ncbi.nlm.nih.gov/20663194/
  19. Tsai CH, Lin LT, Wang CY, Chiu YW, Chou YT, et al. Over-expression of cofilin-1 suppressed growth and invasion of cancer cells is associated with up-regulation of let-7 microRNA. Biochim Biophys Acta. 2015; 1852: 851-861. PubMed: https://pubmed.ncbi.nlm.nih.gov/25597880/
  20. Vlachos IS, Zagganas K, Paraskevopoulou MD, Georgakilas G, Karagkouni D, et al. DIANA-miRPath v3.0: deciphering microRNA function with experimental support. Nucleic Acids Res. 2015; 43: W460-466. PubMed: https://pubmed.ncbi.nlm.nih.gov/25977294/
  21. Nagy A, Lanczky A, Menyhart O, Gyorffy B. Author Correction: Validation of miRNA prognostic power in hepatocellular carcinoma using expression data of independent datasets. Sci Rep. 2018; 8: 11515.
  22. Chen LC, Chang YJ, Chen SJ, Lee WC, Chang CH, et al. Imaging, biodistribution and efficacy evaluation of (188)Re-human serum albumin microspheres via intraarterial route in an orthotopic hepatoma model. Int J Radiat Biol. 2017; 93: 477-486. PubMed: https://pubmed.ncbi.nlm.nih.gov/28045339/
  23. Chang YJ, Hsu CW, Chang CH, Lan KL, Ting G, et al. Therapeutic efficacy of 188Re-liposome in a C26 murine colon carcinoma solid tumor model. Invest New Drugs. 2013; 31: 801-811. PubMed: https://pubmed.ncbi.nlm.nih.gov/23224353/
  24. Tsai CC, Chang CH, Chen LC, Chang YJ, Lan KL, et al. Biodistribution and pharmacokinetics of 188Re-liposomes and their comparative therapeutic efficacy with 5-fluorouracil in C26 colonic peritoneal carcinomatosis mice. Int J Nanomedicine. 2011; 6: 2607-2619. PubMed: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3218575/
  25. Wang SJ, Huang WS, Chuang CM, Chang CH, Lee TW, et al. A phase 0 study of the pharmacokinetics, biodistribution, and dosimetry of (188)Re-liposome in patients with metastatic tumors. EJNMMI Res. 2019; 9: 46. PubMed: https://pubmed.ncbi.nlm.nih.gov/31119414/
  26. Hammond E, Khurana A, Shridhar V, Dredge K. The Role of Heparanase and Sulfatases in the Modification of Heparan Sulfate Proteoglycans within the Tumor Microenvironment and Opportunities for Novel Cancer Therapeutics. Front Oncol. 2014; 4: 195. PubMed: https://pubmed.ncbi.nlm.nih.gov/25105093/
  27. Silver DJ, Siebzehnrubl FA, Schildts MJ, Yachnis AT, Smith GM, et al. Chondroitin sulfate proteoglycans potently inhibit invasion and serve as a central organizer of the brain tumor microenvironment. J Neurosci. 2013; 33: 15603-15617.
  28. Iozzo RV, Sanderson RD. Proteoglycans in cancer biology, tumour microenvironment and angiogenesis. J Cell Mol Med. 2011; 15: 1013-1031. PubMed: https://pubmed.ncbi.nlm.nih.gov/21155971/
  29. Kretschmer A, Moepert K, Dames S, Sternberger M, Kaufmann J, et al. Differential regulation of TGF-beta signaling through SMAD2, Smad3 and Smad4. Oncogene. 2003; 22: 6748-6763. PubMed: https://pubmed.ncbi.nlm.nih.gov/14555988/
  30. Bae DS, Blazanin N, Licata M, Lee J, Glick AB. Tumor suppressor and oncogene actions of TGFbeta1 occur early in skin carcinogenesis and are mediated by Smad3. Mol Carcinog. 2009; 48: 441-453. PubMed: https://pubmed.ncbi.nlm.nih.gov/18942075/
  31. Singha PK, Pandeswara S, Geng H, Lan R, Venkatachalam MA, et al. Increased Smad3 and reduced SMAD2 levels mediate the functional switch of TGF-beta from growth suppressor to growth and metastasis promoter through TMEPAI/PMEPA1 in triple negative breast cancer. Genes Cancer. 2019; 10: 134-149. PubMed: https://pubmed.ncbi.nlm.nih.gov/31798766/
  32. Yang J, Wahdan-Alaswad R, Danielpour D. Critical role of SMAD2 in tumor suppression and transforming growth factor-beta-induced apoptosis of prostate epithelial cells. Cancer Res. 2009; 69: 2185-2190. PubMed: https://pubmed.ncbi.nlm.nih.gov/19276350/
  33. Li C, Nguyen V, Clark KN, Zahed T, Sharkas S, et al. Down-regulation of FZD3 receptor suppresses growth and metastasis of human melanoma independently of canonical WNT signaling. Proc Natl Acad Sci U S A. 2019; 116: 4548-4557. PubMed: https://pubmed.ncbi.nlm.nih.gov/30792348/
  34. Karakas B, Bachman KE, Park BH. Mutation of the PIK3CA oncogene in human cancers. Br J Cancer. 2006; 94: 455-459. PubMed: https://pubmed.ncbi.nlm.nih.gov/16449998/

Figures:

Figure 1

Figure 1

Figure 1

Figure 2

Figure 1

Figure 3

Figure 1

Figure 4

Figure 1

Figure 5

Figure 1

Figure 6

Figure 1

Figure 7

Figure 1

Figure 8

Figure 1

Figure 9

Similar Articles

Recently Viewed

Read More

Most Viewed

Read More

Help ?