METALLOPROTEINASE 9 IN THE TUMOR AND PERITUMORAL TISSUE AS PROGNOSTIC MARKER IN BREAST CANCER PATIENTS

Introduction: Breast cancer is one of the most common malignancies among women all over the world. Tumor microenvironment represents one of the main regulators of tumorigenesis. We investigated the role of matrix metalloproteinases (MMP-9) concentration in peritumoral tissue as a prognostic marker in breast cancer patients. Methods: ELISA test was used to determine total MMP-9 concentration in carcinoma and peritumoral tissue sample in patients with breast cancer. Comparison of MMP-9 protein expression with clinicopathological parameters was evaluated. Results: Peritumoral tissue at 3 cm distance from tumor produces more MMP-9 than the tumor itself. Ratio of concentrations of MMP-9 in tumor and peritumoral tissue considerably changes in favor of peritumoral tissue with the increase of tumor size and involvement of axillary lymph nodes. In N0 stage concentration ratio of MMP-9 in the tumor and peritumoral tissues is 1: 1.44, but in N2 stage ratio is 1: 26.5. Conclusion: In patients with breast cancer even in an early stadium there is a change in MMP-9 concentration in peritumoral tissue. We can extract the group of patients at increased risk for the development of lymph node metastasis. A statistically significant difference between the concentrations of MMP-9 in peritumoral tissue and cancer tissue exists only in the case of metastatic disease.

[1]  G. Melchiorri,et al.  Physical exercise modulates the level of serum MMP-2 and MMP-9 in patients with breast cancer. , 2016, Oncology letters.

[2]  Sanjay Gupta,et al.  p38-MAPK/MSK1-mediated overexpression of histone H3 serine 10 phosphorylation defines distance-dependent prognostic value of negative resection margin in gastric cancer , 2016, Clinical Epigenetics.

[3]  Yuhree Kim,et al.  The role of liver-directed surgery in patients with hepatic metastasis from primary breast cancer: a multi-institutional analysis. , 2016, HPB : the official journal of the International Hepato Pancreato Biliary Association.

[4]  M. Rzeszutko,et al.  Significance of Matrix Metalloproteinase 9 Expression as Supporting Marker to Cytokeratin 19 mRNA in Sentinel Lymph Nodes in Breast Cancer Patients , 2016, International journal of molecular sciences.

[5]  F. Bertucci,et al.  MMP2 and MMP9 serum levels are associated with favorable outcome in patients with inflammatory breast cancer treated with bevacizumab-based neoadjuvant chemotherapy in the BEVERLY-2 study , 2016, Oncotarget.

[6]  M. Szmitkowski,et al.  Plasma Levels and Diagnostic Utility of Macrophage Colony-Stimulating Factor, Matrix Metalloproteinase-9, and Tissue Inhibitor of Metalloproteinases-1 as New Biomarkers of Breast Cancer , 2016, Annals of laboratory medicine.

[7]  L. Gianotti,et al.  Metastatic liver disease from non-colorectal, non-neuroendocrine, non-sarcoma cancers: a systematic review , 2015, World Journal of Surgical Oncology.

[8]  Y. Bao,et al.  Testes-specific protease 50 promotes cell invasion and metastasis by increasing NF-kappaB-dependent matrix metalloproteinase-9 expression , 2015, Cell Death and Disease.

[9]  T. Greulich,et al.  Therapy with Plasma Purified Alpha1-Antitrypsin (Prolastin®) Induces Time-Dependent Changes in Plasma Levels of MMP-9 and MPO , 2015, PloS one.

[10]  S. Iacobelli,et al.  Heregulin-HER3-HER2 signaling promotes matrix metalloproteinase-dependent blood-brain-barrier transendothelial migration of human breast cancer cell lines , 2015, Oncotarget.

[11]  Yves St-Pierre,et al.  MMP-9 expression varies according to molecular subtypes of breast cancer , 2014, BMC Cancer.

[12]  Zhiming Zhang,et al.  Expression and Clinical Significance of Matrix Metalloproteinase-9 in Lymphatic Invasiveness and Metastasis of Breast Cancer , 2014, PloS one.

[13]  B. Song,et al.  Serum levels of matrix metalloproteinase-9 predict lymph node metastasis in breast cancer patients. , 2014, Oncology reports.

[14]  K. Oda,et al.  Matrix Metalloproteinase (MMP)-9 in Cancer-Associated Fibroblasts (CAFs) Is Suppressed by Omega-3 Polyunsaturated Fatty Acids In Vitro and In Vivo , 2014, PloS one.

[15]  James Lee,et al.  Rab40b regulates trafficking of MMP2 and MMP9 during invadopodia formation and invasion of breast cancer cells , 2013, Journal of Cell Science.

[16]  E. Lengyel,et al.  Adipose tissue and adipocytes support tumorigenesis and metastasis. , 2013, Biochimica et biophysica acta.

[17]  Yan Zeng,et al.  Inverse correlation between Naa10p and MMP-9 expression and the combined prognostic value in breast cancer patients , 2013, Medical Oncology.

[18]  J. Ferlay,et al.  Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. , 2013, European journal of cancer.

[19]  Minghui Zhang,et al.  High expression of CD147 and MMP-9 is correlated with poor prognosis of triple-negative breast cancer (TNBC) patients , 2013, Medical Oncology.

[20]  H. Hoekstra,et al.  Radiation-Associated Angiosarcoma After Breast Cancer: High Recurrence Rate and Poor Survival Despite Surgical Treatment with R0 Resection , 2012, Annals of Surgical Oncology.

[21]  A. Paradiso,et al.  Expression of metalloproteinases MMP-2 and MMP-9 in sentinel lymph node and serum of patients with metastatic and non-metastatic breast cancer. , 2010, Anticancer research.

[22]  C. Compton,et al.  The American Joint Committee on Cancer: the 7th Edition of the AJCC Cancer Staging Manual and the Future of TNM , 2010, Annals of Surgical Oncology.

[23]  O. Franco,et al.  Cancer associated fibroblasts in cancer pathogenesis. , 2010, Seminars in cell & developmental biology.

[24]  J. Dietl,et al.  Expression of matrix metalloproteinases (MMPs) in primary human breast cancer and breast cancer cell lines: New findings and review of the literature , 2009, BMC Cancer.

[25]  Bethan Psaila,et al.  The metastatic niche: adapting the foreign soil , 2009, Nature Reviews Cancer.

[26]  G. Lorusso,et al.  The tumor microenvironment and its contribution to tumor evolution toward metastasis , 2008, Histochemistry and Cell Biology.

[27]  A. Theocharis,et al.  Estradiol–estrogen receptor: A key interplay of the expression of syndecan‐2 and metalloproteinase‐9 in breast cancer cells , 2008, Molecular oncology.

[28]  Fei Zhang,et al.  Tumor-derived Matrix Metalloproteinase-13 (MMP-13) correlates with poor prognoses of invasive breast cancer , 2008, BMC Cancer.

[29]  C. Dabrosin,et al.  MMP-2 and MMP-9 activity is regulated by estradiol and tamoxifen in cultured human breast cancer cells , 2007, Breast Cancer Research and Treatment.

[30]  H. Mehdorn,et al.  Differential Expression of Matrix Metalloproteinases in Brain- and Bone-Seeking Clones of Metastatic MDA-MB-231 Breast Cancer Cells , 2006, Journal of Neuro-Oncology.

[31]  M. Björklund,et al.  Gelatinase-mediated migration and invasion of cancer cells. , 2005, Biochimica et biophysica acta.

[32]  A. Roberts,et al.  Breast cancer cells induce stromal fibroblasts to express MMP-9 via secretion of TNF-α and TGF-β , 2005, Journal of Cell Science.

[33]  V. Kosma,et al.  Expression of Matrix Metalloproteinase (MMP)-2 and MMP-9 in Breast Cancer with a Special Reference to Activator Protein-2, HER2, and Prognosis , 2004, Clinical Cancer Research.

[34]  H. Kleinman,et al.  Regulation of heparanase gene expression by estrogen in breast cancer. , 2003, Cancer research.

[35]  S. Eccles,et al.  Expression of matrix metalloproteinases and their inhibitors correlates with invasion and metastasis in squamous cell carcinoma of the head and neck. , 2001, Archives of otolaryngology--head & neck surgery.

[36]  J. Isner,et al.  Estrogen and Angiogenesis: A Review , 2001, Arteriosclerosis, thrombosis, and vascular biology.

[37]  J. Netterville,et al.  Expression of Matrix Metalloproteinases and Tissue Inhibitor of Metalloproteinases in Head and Neck Squamous Cell Carcinoma , 1997, The Annals of otology, rhinology, and laryngology.

[38]  Oliver H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.

[39]  I. Ellis,et al.  Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. , 2002, Histopathology.