Increased expression of matrix metalloproteinases-21 and -26 and TIMP-4 in pancreatic adenocarcinoma

Abstract

Pancreatic adenocarcinoma is known for early aggressive local invasion, high metastatic potential, and a low 5-year survival rate. Matrix metalloproteinases (MMPs) play important roles in tumor growth and invasion. Earlier studies on pancreatic cancer have found increased expression of certain MMPs to correlate with poorer prognosis, short survival time or presence of metastases. We studied the expression of MMP-21, -26, and tissue inhibitor of matrix metalloproteinases ( Keywords: matrix metalloproteinase; adenocarcinoma; tissue inhibitor of metalloproteinase Pancreatic cancer is one of the most lethal types of cancer: the 5-year survival rate of pancreatic adenocarcinoma is under 5%.1,2 Other types of pancreatic tumors (15% of all tumors) include insulinoma, gastrinoma, and carcinoid tumor. Pancreatic cancer is notorious for its late clinical presentation, early and aggressive local invasion, and metastatic potential.3 The diagnosis is confirmed using ultrasound combined with biopsy as well as computed tomography, and tumor markers such as CA 19-9. If metastases are not found, the Whipple operation (pancreaticoduodenectomy) is performed to remove the tumor. If metastases are detected, palliative treatments are chosen, such as biliary bypass procedure or chemo/radiotherapy. A known risk factor for pancreatic cancer is smoking, which increases the risk two-to three-fold. 4 Also, patients with chronic pancreatitis have increased risk for developing pancreatic carcinoma. 5,6

Development of a monoclonal antibody that specifically detects tissue inhibitor of metalloproteinase‐4 (TIMP‐4) in formalin‐fixed, paraffin‐embedded human tissues

“…Therefore, we tested the purified monoclonal antibody for reactivity in a series of tissues. In all tissues tested, we detected a change in expression level comparable to those previously reported [Tunuguntla et al, 2003;Zhao et al, 2004;Lee et al, 2006;Pilka et al, 2006;Ripley et al, 2006;Bister et al, 2007;Hilska et al, 2007]. For example, we detected an increased expression in colon cancer compared to normal tissue and decreased levels of TIMP-4 in pancreatic cancer specimens as compared to normal pancreatic tissue.…”

Lysyl Oxidase (LOX) Transcriptionally Regulates SNAI2 Expression and TIMP4 Secretion in Human Cancers

“…TIMP4 expression has been associated with longer survival in patients with rectal cancer. In addition, elevated levels of TIMP4 have been found in patients with breast, cervical, and prostate cancers, whereas low levels have been found in patients with pancreatic cancer (40)(41)(42). These divergent expression profiles in cancer samples could be due to tissue-specific differences and tumor stages.…”

TIMP-4 and CD63: new prognostic biomarkers in human astrocytomas

“…13 These data suggest that TIMP-4 may be an anti-tumoral factor in gliomas. However, this hypothesis has been challenged by some recent findings in other malignancies, such as breast, prostate, pancreatic and cervical cancers, wherein high TIMP-4 expression has been found 14 to correlate with tumor aggressiveness 15,16 and to stimulate tumorigenic activity. 17 In addition, mounting evidence suggests an independent signaling capacity for tissue inhibitors of metalloproteinases distinct from their matrix metalloproteinase inhibitory activity.…”