The Relationship Among Tumor-associated Macrophages,Matrix Metalloproteinase-9 And Lymphangiogenes In Rectal Cancer

Background and objective:Rectal cancer has a biologic behavior of early lymph node metastasis. The situation of local lymph node metastasis is important in the evaluation of tumor prognosis and treatment protocols. Recently, more lucubrating studies indicated that tumor-associated macrophages (TAM) plays a pivotal role in tumor angiogenesis and lymphangiogenes, which may be a breakthorugh for the mechanism of tumor invasion and metastasis. Matrix metalloproteinase-9 (MMP-9), synthesized by macrophages and some tumor cells, can degrade the main components of the Extracellular matrixc (ECM), which is necessary for lymphatic mircrovessel invasion and lymphangiogenes. Furthermore, matrix metalloproteinase 9 can engender a regenerative feedback to strengthen the capability of the invasiveness and metastasis of tumor cells. Hence, tumor-associated macrophages, MMP-9 and lymphangiogenes could promote lymph node metastasis as a community.In this study, we observed the feature of lymphatic mircrovessels, tumor-associated macrophages disposition and the expression of MMP-9 in the rectal carcinoma, trying to indicate the mechanism of rectal cancer lymphangiogenes by dicussing their relationship, offering theoretical direction and experimenta levidence for clinic therapy.Meterials and methods1,Meter ials:Forty-one patients who had undergone curative resection for rectal carcinoma in the Second Affiliated Hospital of Medical College, Shantou University form August 2007 to August 2008 were included in this study. No patients had received chemotherapy or radiotherapy before surgery. There was no evidence of any other malignancy. The normal mucosa from the distance was also collected as a normal control.2,Methods:SP immunohistochemistrical method and hematoxylineosin staining was used for the detection of the density of lymphatic microvessel(LMVD), density of TAM(TAMD) and the expression of MMP-9.3,All statistical analyses were performed by using the SPSS software package (version 16.0; SPSS, Inc., Chicago, IL, USA).Results1. Lymphangiogenes existed mainly in peritumoral tissues (LMVD 14.0244±1.5422) and statistical significance was observed between the positive control group and the normal control group. The LMVD was associated with tumor Dukes stages, lymphatic mircrovessels invasion and lymph node metastasis.2. The infiltration of TAM mainly existed in the mesenchyma edging the nests and statistical significance was observed between the positive control group and the normal control group. The TAMD was associated with tumor size, Dukes stages, lymphatic mircrovessels invasion and lymph node metastasis.3. The exprssion of MMP-9 was mainly detected in both of the nest and the perienchyma (Positive rate 80.5%). Statistical significance was observed between the positive control group and the normal control group. The positive expression of MMP-9 was associated with tumor Dukes stages, the differentiation of tumor cells and lymph node metastasis.4. The level of MMP-9 exprssion was synchronous with the invasion of tam. The level of MMP-9 expression was associated with lymphangiogenes and statistical signifi-cance was observed. TAMD and LMVD is obviously linear. (R=0.605, Y= 0.410*X+2.873, P<0.001)Conclusions 1. The lymphangiogenes of rectal cancer happened mainly in peritumoral tissues, the morphological and distributing feature of lymphatic mircrovessels might be the anatomic basis of lymhatic metastasis in rectal cancer.2. The intercellular substance of rectal cancer, which is infiltrated by plenty of TAM, is an inflammatory microenvironment in virtually, and TAMD contribute to lymphatic microvessel density in rectal cancer.3. Both the rectal cancer cell and intercellular substance can express MMP-9, the expression of MMP-9 can induce the lymphangiogenes.4. There might have a regenerative feedback existing among MMP-9, tumor-associated macrophages and lymphangiogenes in rectal cancer, they attribute to the development and metastasis of cancer jointly.5. The anti-inflammatory therapy aim at TAM might be a way in effect to reduce lymph node metastasis in rectal cancer.