Expression of Integrin α5, α6, αV, β1, β3, β4 Subunits in Gastric Cancer

Background/Aims: The integrins play a central role in maintaining the morphology of cell and tissue, growth, differentiation, migration, survival and apoptosis of cells, and angiogenesis. Although integrins are implicated in carcinogenesis and tumor angiogenesis, their precise contributions to the process are largely unknown. Methods: For paraffin embedded tissue samples of 102 gastric cancers (23 differentiated, 79 undifferentiated), the expression of integrin α5, α6, αV, β1, β3, β4 subunits and factor VIII were examined by immunohistochemical staining. The relationships between the expression of each integrin and several clinicopathologic parameters were analyzed. Results: The positive rates of integrins were as follows: α5 24%, β1 8%, α6 16%, β4 24%, αV 29%, and β3 34%. The expression of α5, α6, and αV was well correlated with the expression of β1, β4, and β3, respectively. The αV integrin was highly expressed in tumors of advanced T stage. The expressions of α6 and β4 integrins were significantly higher in differentiated tumors, but the β3 integrin was significantly expressed in undifferentiated tumors. The number of tumor vessels has positive correlation with αV integrin expression. Conclusions: These findings suggest that integrin α6β4 is one of the key factors in determining tumor differentiation and growth pattern. The integrin αVβ3 may be related to the angiogenesis especially in advanced gastric cancer.ope

Thymidine phosphorylase 과발현이 췌장암 세포 악성화에 미치는 역할 규명

Brain Korea 21 Project for Medical Sciences/석사[한글] Thymidine phosphorylase(TP)는 혈관 생성인자로서 혈관내피세포에 대한 주화인자 및 성장인자로 그 역할이 규명된 이래 다양한 암 및 만성 염증 부위의 혈관형성 원인으로서 그 역할이 증명되었다. 최근에는 TP가 종양의 성장, 주변조직으로의 침윤 및 전이와 상관관계가 있다고 보고되고 있다. 그러나 아직까지 TP에 의한 췌장암 에서의 역할은 거의 알려진바 없다. 본 연구에서는 췌장암 세포인 Panc-1 세포에 TP 유전자를 이입하여 TP를 과발현 하였을 때 세포성장에 미치는 영향 규명과 이와 관련된 세포신호전달 인자의 발현변화를 관찰하였다. 그 결과 TP 과발현 세포에서 대조군에 비하여 세포의 침윤성 및 이동성이 증가함을 관찰하였으며, 세포의 이동성과 관련된 단백인 RhoA와 MMP2의 발현이 동시에 증가함을 관찰하였다. 아울러 TP가 과발현 되었을 때 대조군에 비해 세포의 증식 속도가 현저히 증가하였으며, 이는 과발현된 TP에 의해 세포주기 중 G0/G1 주기에서 S 주기로의 이행을 촉진한 결과임을 규명하였다. 이와 같은 결과는 췌장암세포에서 thymidine phosphorylase 과발현이 세포의 침윤성 및 이동성 증가와 함께 세포 성장을 촉진시킴으로써 보다 악성화된 세포의 종양생물학적 특성을 야기하며, 이를 이용한 췌장암에서의 암전이 연구 및 새로운 항암치료제 개발로의 응용 연구가 필요할 것으로 생각된다. [영문] Thymidine phosphorylase(TP), originally isolated from platelets, was also known as platelet-dervied endothelial growth factor (PD-ECGF) based on its ability to induce proliferation of endothelial cell in vitro. TP previously known only for its role in nucleotide salvage is an angiogenesis inducing factor and endothelial cell chemoattractant. TP expression is elevated in many solid tumors and in chronically inflammed tissues both known areas of active angiogenesis. In addition, recent clinicopathological immunohistochemstry outcomes showed the correlation between TP overexpression and poor prognosis of cancer due to invasion and metastasis. However, the role of TP on carcinogenesis, progression or metastasis of pancreatic cancer still have not been investigated. The aim of this study is to investigate the role of TP overexpression in the growth, invasion, and migration of pancreatic cancer cell, Panc-1, in vitro with observing the differences between cells transfected with of TP cDNA construct (Panc-1/TP) and vector alone (Panc-1/Mock), The results showed that TP overexpression enhanced the ability of invasion and migration characteristics of pancreatic cancer cells in vitro. This is associated with increased RhoA expression. TP overexpression also accelerated the cell proliferation via shortening of doubling time and early entry of S-phase resulting in rapid cell cycle progression in pancreatic cancer cells. These in vitro results are in agreement with a number of previous clinico-pathological immunohistochemistry observations. Taken together, TP might be the important factor that forces the growth and aggressiveness of pancreatic cancer.prohibitio