Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

Effects of Differential Distribution of Microvessel Density, Possibly Regulated by miR-374a, on Breast Cancer Prognosis

  • Li, Jian-Yi (Department of Breast Surgery, Shengjing Hospital of China Medical University) ;
  • Zhang, Yang (Department of Breast Surgery, Shengjing Hospital of China Medical University) ;
  • Zhang, Wen-Hai (Department of Breast Surgery, Shengjing Hospital of China Medical University) ;
  • Jia, Shi (Department of Breast Surgery, Shengjing Hospital of China Medical University) ;
  • Kang, Ye (Department of Breast Surgery, Shengjing Hospital of China Medical University) ;
  • Tian, Rui (Department of Breast Surgery, Shengjing Hospital of China Medical University)
  • Published : 2013.03.30
Download PDF
⟨ Previous Next ⟩

Abstract

Background: The discovery that microRNAs (miRNAs) regulate proliferation, invasion and metastasis provides a principal molecular basis of tumor heterogeneity. Microvessel distribution is an important characteristic of solid tumors, with significant hypoxia occurring in the center of tumors with low blood flow. The distribution of miR-374a in breast tumors was examined as a factor likely to be important in breast cancer progression. Methods: Breast tissue samples from 40 patients with breast cancer were classified into two groups: a highly invasive and metastatic group (HIMG) and a low-invasive and metastatic Group (LIMG). Samples were collected from the center and edge of each tumor. In each group, six specimens were examined by microRNA array, and the remaining 14 specimens were used for real-time RT-qPCR, Western blot and immunohistochemical analyses. Correlation analysis was performed for the miRNAs and target proteins. Follow-up was carried out during 28 months to 68 months after surgery, and survival data were analyzed. Results: In the LIMG, the relative content of miR-374a was lower in the center of the tumor than at its edge; in the HIMG, it was lower at the edge of the tumor, and miR-374a levels were lower in breast cancer tissues than in normal tissues. There was no difference between VEGF-A and VCAM-1 mRNA levels at the edge and center of the tumor; however, we observed a significant difference between VEGF-A and VCAM-1 protein expression levels in these two regions. There was a negative correlation between miR-374a and target protein levels. The microvessel density (MVD) was lower in the center of the tumor than at its edge in HIMG, but the LIMG vessels were uniformly distributed. There was a significant positive correlation between MVD and the number of lymph node metastases (Pearson correlation, r=0.912, P<0.01). The median follow-up time was 48.5 months. LIMG had higher rate of disease-free survival (100%, P=0.013) and longer median survival time (66 months) than HIMG, which had a lower rate of 75% and shorter median survival time (54 months). Conclusions: Our data demonstrated miR-374a to be differentially distributed in breast cancer; VEGF-A and VCAM-1 mRNA had coincident distribution, and the distribution of teh respective proteins was uneven and opposite to that for the miR-374a. These data might explain the differences in the distribution of MVD in breast cancer and variation in breast cancer prognosis.

Keywords

References

  1. Balsat C, Blacher S, Signolle N, et al (2011). Whole slide quantification of stromal lymphatic vessel distribution and peritumoral lymphatic vessel density in early invasive cervical cancer: a method description. ISRN Obstet Gynecol, 25, 1-7.
  2. Biesaga B, Niemiec J, Ziobro M (2012). Microvessel density and status of p53 protein as potential prognostic factors for adjuvant anthracycline chemotherapy in retrospective analysis of early breast cancer patients group. Pathol Oncol Res, 18, 949-60. https://doi.org/10.1007/s12253-012-9525-9
  3. Blackwell KL, Dewhirst MW, Liotcheva V, et al (2004). HER-2 gene amplification correlates with higher levels of angiogenesis and lower levels of hypoxia in primary breast tumors. Clin Cancer Res, 10, 4083-8. https://doi.org/10.1158/1078-0432.CCR-03-0695
  4. Cao Y, E G, Wang E, et al (2012). VEGF exerts an angiogenesisindependent function in cancer cells to promote their malignant progression. Cancer Res, 72, 3912-8. https://doi.org/10.1158/0008-5472.CAN-11-4058
  5. Caporali A, Emanueli C (2011). MicroRNA regulation in angiogenesis. Vascul Pharmacol, 55, 79-86. https://doi.org/10.1016/j.vph.2011.06.006
  6. Crossin KL (2012). Oxygen levels and the regulation of cell adhesion in the nervous system: A control point for morphogenesis in development, disease and evolution? Cell Adh Migr, 6, 49-58. https://doi.org/10.4161/cam.19582
  7. de Jong JS, van Diest PJ, Baak JP (2000). Hot spot microvessel density and the mitotic activity index are strong additional prognostic indicators in invasive breast cancer. Histopathology, 36, 306-12. https://doi.org/10.1046/j.1365-2559.2000.00850.x
  8. Ding YB, Chen GY, Xia JG, et al (2003). Association of VCAM-1 overexpression with oncogenesis, tumor angiogenesis and metastasis of gastric carcinoma. World J Gastroenterol, 9, 1409-14.
  9. Jakobisiak M, Lasek W, Golab J (2003). Natural mechanisms protecting against cancer. Immunol Lett, 90, 103-22. https://doi.org/10.1016/j.imlet.2003.08.005
  10. Kanjanapanjapol S, Wongwaisayawan S, Phuwapraisirisan S, et al (2007). Prognostic significance of microvessel density in breast cancer of Thai women. J Med Assoc Thai, 90, 282-90.
  11. Kwong A, Mang OW, Wong CH, et al (2011). Breast cancer in Hong Kong, Southern China: the first population-based analysis of epidemiological characteristics, stage-specific, cancer-specific, and disease-free survival in breast cancer patients: 1997-2001. Ann Surg Oncol, 18, 3072-8. https://doi.org/10.1245/s10434-011-1960-4
  12. Linderholm B, Lindh B, Tavelin B, et al (2000). p53 and vascular-endothelial-growth-factor (VEGF) expression predicts outcome in 833 patients with primary breast carcinoma. Int J Cancer, 89, 51-62. https://doi.org/10.1002/(SICI)1097-0215(20000120)89:1<51::AID-IJC9>3.0.CO;2-8
  13. Mackey JR, Kerbel RS, Gelmon KA, et al (2012). Controlling angiogenesis in breast cancer: A systematic review of antiangiogenic trials. Cancer Treat Rev, 38, 673-88. https://doi.org/10.1016/j.ctrv.2011.12.002
  14. Patella F, Rainaldi G (2012). MicroRNAs mediate metabolic stresses and angiogenesis. Cell Mol Life Sci, 69, 1049-65. https://doi.org/10.1007/s00018-011-0775-6
  15. Pritchard CC, Cheng HH, Tewari M (2012). MicroRNA profiling: approaches and considerations. Nat Rev Genet. 13, 358-69. https://doi.org/10.1038/nrg3198
  16. Rapisarda A, Melillo G (2012). Role of the VEGF/VEGFR axis in cancer biology and therapy. Adv Cancer Res, 114, 237-67. https://doi.org/10.1016/B978-0-12-386503-8.00006-5
  17. Tassi E, McDonnell K, Gibby KA, et al (2011). Impact of fibroblast growth factor-binding protein-1 expression on angiogenesis and wound healing. Am J Pathol, 179, 2220-32. https://doi.org/10.1016/j.ajpath.2011.07.043
  18. Võsa U, Vooder T, Kolde R, et al (2011). Identification of miR-374a as a prognostic marker for survival in patients with early-stage nonsmall cell lung cancer. Genes Chromosomes Cancer, 50, 812-22. https://doi.org/10.1002/gcc.20902

Cited by

  1. Down-regulation of miRNA-452 is Associated with Adriamycin-resistance in Breast Cancer Cells vol.15, pp.13, 2014, https://doi.org/10.7314/APJCP.2014.15.13.5137
  2. Different types of tumor vessels in breast cancer: morphology and clinical value vol.4, pp.1, 2015, https://doi.org/10.1186/s40064-015-1293-z
  3. Effects of receptor for advanced glycation endproducts on microvessel formation in endometrial cancer vol.16, pp.1, 2016, https://doi.org/10.1186/s12885-016-2126-3
  4. miR-374a-CCND1-pPI3K/AKT-c-JUN feedback loop modulated by PDCD4 suppresses cell growth, metastasis, and sensitizes nasopharyngeal carcinoma to cisplatin vol.36, pp.2, 2017, https://doi.org/10.1038/onc.2016.201
  5. F]Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography of Non–Small Cell Lung Carcinoma and Its Relationship to Metabolic Parameters and Pathologic Staging vol.13, pp.9, 2014, https://doi.org/10.2310/7290.2014.00032
  6. Dual roles of miR-374a by modulated c-Jun respectively targets CCND1-inducing PI3K/AKT signal and PTEN-suppressing Wnt/β-catenin signaling in non-small-cell lung cancer vol.9, pp.2, 2018, https://doi.org/10.1038/s41419-017-0103-7
  7. Age-related microRNAs in older breast cancer patients: biomarker potential and evolution during adjuvant chemotherapy vol.18, pp.1, 2018, https://doi.org/10.1186/s12885-018-4920-6