Thrombospondin-1 (TSP-1) is widely distributed in human tissues and is important in inhibiting angiogenesis.It also occupies an indispensable position in the formation, growth, differentiation, and metastasis of tumors in different tissues.TSP-1 plays an important role in the occurrence and development of various types of tumors. The inhibitory effect of TSP-1 on the angiogenesis and tumor development of oral and maxillofacial malignant tumors has been demonstrated in recent years. This paper reviews the findings and progress of TSP-1 research involving all kinds of tumors as well as oral and maxillofacial malignancies.
Humans ; Neoplasms ; Neovascularization, Pathologic ; Thrombospondin 1

OBJECTIVE: We investigated the expression of TSP-1 and -2 in eutopic endometrium of advanced endometriosis and control patients. METHODS: The 33 endometriosis patients and 32 controls were enrolled. Endometrial samples were obtained from 65 premenopausal women aged 29-44 years, undergoing laparoscopic surgery or hysterectomy for non-malignant lesions. Sufficient samples were collected from 33 patients with endometriosis stage III and IV and 32 controls without endometriosis confirmed by laparoscopic surgery. The mRNA expression from eutopic endometrium for TSP-1 and -2 were analyzed by RT-QC PCR. RESULTS: The mRNAs of TSP-1 and -2 were expressed in eutopic endometrium from endometriosis and normal controls throughout the menstrual cycle. There were no significant differences in expression of TSP-1 and TSP-2 in eutopic endometrium between controls and endometriosis patients. CONCLUSION: Our results indicated that TSP-1 and -2 had no crucial role compared to other molecules in the regulation of angiogenesis. These findings also suggest that dysregulation of other angiogenic regulators would be concerned in pathophysiologic role in endometriosis development.
Endometriosis* ; Endometrium ; Female ; Humans ; Hysterectomy ; Laparoscopy ; Menstrual Cycle ; Polymerase Chain Reaction ; RNA, Messenger* ; Thrombospondin 1 ; Thrombospondins

PURPOSE: The precise role of angiogenesis in prostate cancer should be defined. Several reports suggest that thrombospondin-1 (TSP-1) possesses a tumor suppressor function, possibly through its ability to inhibit tumor neovascularization. The vascular endothelial growth factor (VEGF), one of the most important angiogenic factors in a solid tumor, has shown conflicting results on prostate cancer. Therefore, TSP-1 and VEGF expression in prostate cancer, and their relationship with the p53 status were analyzed. MATERIALS AND METHODS: Using immunohistochemistry, the expression of VEGF, TSP-1 and p53 was assessed in 75 archival tissues from 23 benign prostatic hyperplasia (BPH), 22 localized prostate cancer, and 30 metastatic prostate cancer patients. The relationship between VEGF and TSP-1, and the p53 status, tumor grade and stage was evaluated in patients with prostate cancer. RESULTS: The immunohistochemical analysis demonstrated a higher VEGF expression level (p<0.01) and a lower TSP-1 expression level (p<0.01) in prostate cancer compared to the BPH tissues. In addition, a higher VEGF expression level (p<0.05) and a lower TSP-1 expression level (p<0.05) in metastatic prostate cancer tissues were observed compared to the localized prostate cancer tissues. A significant inverse correlation was found between the TSP-1 and VEGF expression levels. There was a significant association between the VEGF expression level and the p53 status (p<0.05), but the TSP-1 expression level was not associated with the p53 status. CONCLUSIONS: These results show that angiogenic factors including VEGF and TSP-1 might play an important role in the development and progression of prostate cancer. These changes appear to be influenced by the p53 status.
Angiogenesis Inducing Agents ; Humans ; Immunohistochemistry ; Prostate* ; Prostatic Hyperplasia* ; Prostatic Neoplasms* ; Thrombospondin 1 ; Vascular Endothelial Growth Factor A*

PURPOSE: The exact role of angiogenesis in prostate cancer is unknown. We investigated whether endocrine therapy inhibits angiogenesis, and influences the expression of thrombospondin-1 (TSP-1), a potent inhibitor of angiogenesis, and vascular endothelial growth factor (VEGF) in prostate cancer. MATERIALS AND METHODS: Employing immunohistochemistry, we assessed the expression of VEGF and TSP-1 in archival tissues from 46 patients with metastatic prostate cancer (30 before androgen deprivation therapy and 16 after at least 6-months' duration of androgen deprivation therapy). For each tumour, microvascular density (MVD) counts were determined using immunohistochemical staining for factor VIII. The relationship between MVD and the expression of VEGF and TSP-1, the tumour grade was assessed in metastatic prostate cancer. RESULTS: The mean MVD counts (71.1 vessels per 200x high-power field) in 16 patients with metastatic cancer after androgen deprivation therapy was significantly higher than that (51.7) in 30 patients before androgen deprivation therapy (p<0.05). The immunohistochemical analysis demonstrated a higher TSP-1 expression (p<0.01), and a lower VEGF expression (p<0.01), in androgen deprivation group. There was no significant correlation between VEGF or TSP-1 expression and the mean MVD counts. The MVD counts had no correlation with Gleason scores or initial PSA levels. CONCLUSIONS: Endocrine therapy in metastatic prostate cancer significantly decreased MVD counts, the expression of VEGF and significantly increased the expression of TSP-1. The present study shows that decreased angiogenesis including changes in the expressions of angiogenic factors, might have an important role in the therapeutic effect of androgen deprivation in metastatic prostate cancer.
Angiogenesis Inducing Agents ; Factor VIII ; Humans ; Immunohistochemistry ; Prostate* ; Prostatic Neoplasms* ; Thrombospondin 1 ; Vascular Endothelial Growth Factor A*

OBJECTIVETo study the expression of inhibitor-1 of DNA binding/differentiation-1 (Id-1) and thrombospondin-1 (TSP-1) genes in mucoepidermoid carcinoma of different malignant degree and analyze the relationship between them.

METHODSUsing immunohistochemistry (IHC) staining technique, TSP-1 and Id-1 proteins in the mucoepidermoid carcinoma of different malignant degree, including well-differentiated, moderately differentiated and poorly differentiated mucoepidermoid carcinoma, and normal salivary gland tissues were detected.

RESULTSThe positive rate of Id-1 and TSP-1 in normal salivary glands were apparently lower than that in malignant mucoepidermoid carcinoma(P = 0.000, P = 0.013). The positive rate of Id-1 in moderately and poorly differentiated mucoepidermoid carcinoma was higher than that of the well-differentiated (P = 0.001, P = 0.002). However, the positive expression of Id-1 showed no relationship between the moderately and poorly differentiated mucoepidermoid carcinoma(P > 0.05). The positive rate of TSP-1 in poorly differentiated mucoepidermoid carcinoma was less than that of the well-differentiated(P = 0.014). The positive expression of TSP-1 showed no relationship between the moderately and poorly differentiated mucoepidermoid carcinoma(P > 0.05), and the positive expression of it also showed no relationship between the moderately and well differentiated mucoepidermoid carcinoma (P > 0.05). The expression of Id-1 and TSP-1 showed negative correlation(r = -0.394, P = 0.002).

CONCLUSIONThe expression of TSP-1 may inhibit the development of the mucoepidermoid carcinoma, contrarily, the expression of Id-1 may prompt the development of the mucoepidermoid carcinoma. The expression of Id-1 and TSP-1 has negative correlation.

Cell Adhesion Molecules ; metabolism ; Extracellular Matrix Proteins ; metabolism ; Humans ; Neoplasms ; metabolism ; pathology ; Thrombospondin 1 ; metabolism

OBJECTIVE: To explore the changes of Ⅻ antithrombin (FⅫa-AT), thrombospondin-1 (TSP-1), and lupus anticoagulant (LA) ratio in the peripheral blood factor of patients with systemic lupus erythematosus (SLE) and the clinical value of combined diagnosis of thrombotic events. METHODS: A total of 133 SLE patients treated in Xingtai People's Hospital were selected and divided into simple SLE group (105 cases) and SLE complicated with thrombosis group (28 cases) according to whether thrombotic events occurred, and 102 cases of healthy people in the same period were selected as control. The clinical data of the 3 groups, the level of peripheral blood FⅫa-AT, TSP-1, and LA ratio were compared, the relationship between each peripheral blood index and SLE disease activity index (SLEDAI) score were analyzed. The influencing factors of thrombotic events in SLE patients were analyzed, and the value of each peripheral blood index in the diagnosis of SLE complicated with thrombotic events were evaluated. RESULTS: The proportion of the patients with age ≥60 year, hypertension, and smoking history in SLE complicated with thrombosis group was higher than those in simple SLE group and control group (P＜0.05). The SLEDAI score, peripheral blood FⅫa-AT, TSP-1, LA ratio levels of the patients in SLE complicated with thrombosis group were significantly higher than those in simple SLE group and control group, and the simple SLE group was significantly higher than the control group (P＜0.05). FⅫa-AT, TSP-1, LA ratio in peripheral blood of SLE patients were positively correlated with SLEDAI score (r=0.663, 0.578 and 0.625). Age, blood pressure, smoking history, peripheral blood FⅫa-AT, TSP-1, LA ratio were the important influencing factors of thrombotic events in SLE patients (P＜0.05). The AUC diagnosed by the FⅫa-AT, TSP-1, and LA ratio in peripheral blood was 0.881, the 95% CI was 0.813-0.931, the sensitivity was 82.14%, and the specificity was 91.43%, which was superior to each index alone (P＜0.05). CONCLUSION Peripheral blood FⅫa-AT, TSP-1, LA ratio level changes in SLE patients are significantly related to disease activity, and the combined diagnosis of thrombotic events is more reliable.
Humans ; Lupus Erythematosus, Systemic/complications* ; Risk Factors ; Thrombosis/etiology* ; Thrombospondin 1

Thrombospondin-1 (TSP-1), a multifunctional extracellular matrix protein, inhibits neovascularization and is implicated in the regression of tumor growth and metastasis. We found that the synthesis of TSP-1 in porcine aortic endothelial (PAE) cells was decreased in a dose-dependent manner by phorbol 12-myristate 13-acetate (PMA) treatment in porcine aortic endothelial (PAE) cells. In this study, a responsive site on the TSP-1 promotor affected by PMA treatment in PAE was characterized. The level of TSP-1 mRNA was also decreased by PMA after 1 h and persisted that way for at least 24 h. PMA treatment and c-Jun overexpression suppressed the transcription of TSP-1 promotor-luciferase reporter gene. A deletion between -767 and -657 on the TSP-1 promotor neutralized the PMA-induced down-regulation. In addition, oligo a (-767 approximately -723) was responsive to PMA-induced repression, while oligo b (-734 approximately -689) and c (-700 approximately -656) was not. Electrophoretic mobility shift assays showed that this PMA responsive element specifically bound a nuclear protein and that the binding activity was diminished by PMA treatment in PAE cells but not in Hep 3B cells. In supershift assay, potential regulatory elements in this region, SP1 and GATA-1, were not responsive to the inhibition of TSP-1 expression by PMA. Our results suggest that the repression of TSP-1 synthesis by PMA is mediated by blocking a particular unknown nuclear protein binding to the responsive site (-767 approximately -735), which is regulated by c-Jun.
Animal ; Aorta/cytology ; Cell Line ; Down-Regulation (Physiology) ; Endothelium, Vascular/drug effects* ; Endothelium, Vascular/cytology ; Promoter Regions (Genetics)* ; Proto-Oncogene Proteins c-jun/metabolism ; Response Elements* ; Swine ; Tetradecanoylphorbol Acetate/pharmacology* ; Thrombospondin 1/genetics* ; Thrombospondin 1/biosynthesis

OBJECTIVE: Vascular Endothelial Growth Factor (VEGF) is a potent stimulator of angiogenesis in solid tumors. Thrombospondin-1 (TSP-1) has inhibitory role in cancer cell proliferation and metastasis. To analyze the correlation with expression of VEGF and TSP-1 including microvessel density (MVD), the levels of VEGF/TSP-1 mRNA expression and microvessel count (MVC) were estimated in patients with invasive cervical carcinomas. METHODS: From 1996 to 1999, 37 carcinomas and 7 normal cervical tissues were collected, frozen and stored at -70 degrees C until used. The levels of VEGF and TSP-1 mRNAs were determined by quantitative RT-PCR. MVD was assessed by immunostaining for factor VIII-related antigen. The results are expressed as the largest number of microvessels present within a single x 40 field, and counted at x 100 field. RESULTS: Quantitative RT-PCR analysis demonstrated abnormally increased VEGF mRNA expression levels (>0.66) in 14 (37.8%) of 37 cervical carcinomas comparing to control groups (mean: 0.32+/-0.09) and abnormally low TSP-1 mRNA expression levels (<0.72) in 13 (35.1%) of 37 cervical carcinomas comparing to control groups (mean: 0.51+/-0.07). MVC was higher in tumors showing decreased expression of TSP-1 (but not statistically) (p<0.18) and overexpression of VEGF (p<0.05). When VEGF overexpression was accompanied with reduced TSP-1 expression, the microvessel density showed significantly increased pattern (p<0.05). CONCLUSION: Our study demonstrates that reduced expression of TSP-1 mRNAs and overexpression of VEGF mRNAs may be an important contributing factor in cervical carcinomas. Moreover, the inversed correlation of VEGF and TSP-1 mRNA expression can be an evidence of angiogenic role in cervical carcinomas.
Cell Proliferation ; Humans ; Microvessels* ; Neoplasm Metastasis ; RNA, Messenger* ; Thrombospondin 1 ; Uterine Cervical Neoplasms ; Vascular Endothelial Growth Factor A* ; von Willebrand Factor

PURPOSE: With the process of neoangiogenesis being linked to the growth and metastasis of various tumors, anticancer therapeutics with a basis in the suppression of neoangiogenesis has recently been receiving attention. In this study, we tried to clarify the immunoreactivities of vascular endothelial growth factor (VEGF), major angiogenic inducer and thrombospondin-1 (TSP-1), major angiogenic inhibitor in human Wilms' tumor and its clinicopathological significance. MATERAILS AND METHODS: Utilizing immunohistochemical staining, we assessed the immunoreactivities of VEGF and TSP-1 in archival tissues of 29 Wilms' tumors and 25 normal kidneys. Also, we assessed the relationship between expression of each factor and clinicopathological parameters in 29 cases of Wilms' tumors. RESULTS: Immunoreactivities of VEGF and TSP-1 were detected mainly in the cytoplasm of the tubular cells in normal kidneys. In Wilms' tumors, whereas VEGF was detected in the cytoplasm of the tumor cells and peritumoral stromal tissues, but TSP-1 only in the peritumoral stromal tissues. Immunohistochemical expression patterns of each factor were divided into two groups according to the area of immunoreactivity (negative:<10%, positive: > OR =10%). VEGF immunoreactivity was detected in 25 (100%) normal kidneys and in 20 (69%) Wilms' tumors. However, TSP-1 immunoreactivity was detected in 24 (97%) normal kidneys and in 3 (10%) Wilms' tumors. Therefore, although no significant difference was observed between the expressions of VEGF and TSP-1 in normal kidney, the TSP-1 immunoreactivity was significantly lower than VEGF immunoreactivity in Wilms' tumors. A relatively higher rate of positive expression of TSP-1 was observed in the patients with no demonstrable lymph node metastasis. Also, as for the VEGF, maximal diameter of the tumor was larger in the positive expression group. However, it proved otherwise for TSP-1 as the negative expression group demonstrated tumors with larger maximal diameters. CONCLUSIONS: Our study demonstrated that the TSP-1 immunoreactivity was significantly lower than VEGF immunoreactivity in Wilms' tumors, and disease progression has a tendency to be found in the VEGF-positive cases and TSP-1 negative cases. We suggest that the growth and metastasis of Wilms' tumor may be influenced mainly by TSP-1 decrease rather than VEGF increase.
Cytoplasm ; Disease Progression ; Humans ; Kidney ; Lymph Nodes ; Neoplasm Metastasis ; Thrombospondin 1 ; Vascular Endothelial Growth Factor A* ; Wilms Tumor*