Thrombospondin 2 expression is correlated with inhibition of angiogenesis and metastasis of colon cancer

Tokunaga, Tetsuji; Nakamura, Masato; Oshika, Y; Abe, Yoshiyuki; Ozeki, Yuichi; Fukushima, Yasushi; Hatanaka, Hiroyuki; Sadahiro, Sotaro; Kijima, Hiroshi; Tsuchida, Takashi; Yamazaki, Hitoshi; Tamaoki, Norikazu; Ueyama, Yoshito

doi:10.1038/sj.bjc.6690056

Cited by 102 publications

(82 citation statements)

References 38 publications

(32 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…27). Thrombospondin expression did not correlate with pathologic features of the primary colorectal tumor, as shown by other researchers (4,5,28,29).…”

Section: Discussionsupporting

confidence: 58%

“…To analyze the roles of both TSP-1 and TSP-2 in the risk of the development of liver metastases, Tokunaga et al, in a study of 61 patients with colorectal cancer (28), found TSP-1 gene expression in 6.5% of primary tumors, TSP-2 gene expression in 28% of tumors, and gene expression of both markers in 34% of tumors. Both thrombospondin genes were more significantly expressed in the primary tumor than in the surrounding tissue.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Expression of Thrombospondin-1 in Resected Colorectal Liver Metastases Predicts Poor Prognosis

Sutton¹,

O’Byrne²,

Goddard³

et al. 2005

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: The aim of this study was to examine the expression and prognostic relevance of thrombospondin-1 (TSP-1) in tumor biopsies taken from a consecutive series of liver resections done at the University Hospitals of Leicester and the Royal Liverpool Hospital. Experimental Design: Patients having undergone a liver resection for colorectal liver metastases at our institutions between 1993 and 1999 inclusive were eligible. Inclusion criteria were curative intent, sufficient tumor biopsy, and patient follow-up data. One hundred eighty-two patients were considered in this study. Standard immunohistochemical techniques were used to study the expression of TSP-1 in 5-Am tumor sections from paraffin-embedded tissue blocks. TSP-1 was correlated with survival using the Kaplan-Meier method and log-rank test for univariate analysis and the Cox proportional hazard model for multivariate analysis. Results: One hundred eighty-two patients (male, n = 122 and female, n = 60) ages between 25 and 81 years (mean, 61 years) were included. TSP-1 was expressed around blood vessels (n = 45, 25%) or in the stroma (n = 59, 33%). No expression was detected in the remaining tumors. TSP-1 significantly correlated with poor survival on univariate (P = 0.01 for perivascular expression and P = 0.03 for stromal expression) and multivariate analysis (P = 0.01 for perivascular expression). Conclusion: TSP-1 is a negatively prognostic factor for survival in resected colorectal liver metastases.Thrombospondin-1 (TSP-1) is a multidomain glycoprotein that modulates platelet aggregation, wound healing, protease activity, and cellular functions such as adhesion, motility, and growth (1). However, the precise function of TSP-1 in the growth of tumors is not straightforward. Evidence suggests that different fragments of the large TSP-1 molecule may individually facilitate different and opposing tumor-modulating properties, such as proangiogenic and antiangiogenic activity (2) and promotion/inhibition of tumor cell migration (3).In colorectal cancer, TSP-1 has been shown to have both an antiangiogenic effect (4, 5) and conversely be associated with venous invasion and tumor progression (6). However, expression of TSP-1 has been associated with increased disease-free survival rates: 84% 5-year survival in primary colorectal tumors expressing TSP-1 compared with 55% in TSP-1-negative tumors in one study (4) and 91% survival versus 44% in TSP-1-negative tumors in another study (5). Studies in breast cancer have described reduced TSP-1 levels in association with more aggressive tumors (3). It is noteworthy that these figures pertain to studies carried out in primary tumors. The aim of this study was to examine the expression and prognostic relevance of TSP-1 in resected colorectal liver metastases.

show abstract

“…27). Thrombospondin expression did not correlate with pathologic features of the primary colorectal tumor, as shown by other researchers (4,5,28,29).…”

Section: Discussionsupporting

confidence: 58%

Section: Discussionmentioning

confidence: 99%

Expression of Thrombospondin-1 in Resected Colorectal Liver Metastases Predicts Poor Prognosis

Sutton¹,

O’Byrne²,

Goddard³

et al. 2005

Clinical Cancer Research

View full text Add to dashboard Cite

show abstract

“…Tumor MVD is a significant and independent prognostic indicator for relapse-free and overall survival of cancer patients [152]. Similarly, elevated tumor or serum levels of the pro-angiogenic factors VEGF-A, interleukin (IL) and FGF-2 as well as a low ratio between the angiogenesis inhibitor thrombospondin-2 and VEGF-A are associated with an increased incidence of metastasis in cancer patients [153][154][155]. Xenograft animal models confirm the correlation of tumoral overexpression of angiogenic growth factors, increased MVD of primary and secondary tumors and metastasis formation [156][157][158].…”

Section: Tumor Angiogenesismentioning

confidence: 99%

Metastasis: cell-autonomous mechanisms versus contributions by the tumor microenvironment

Kopfstein

Christofori

2006

Cell. Mol. Life Sci.

207

160

View full text Add to dashboard Cite

Abstract. The fatality of cancer predominantly results from the dissemination of primary tumor cells to distant sites and the subsequent formation of metastases. During tumor progression, some of the primary tumor cells as well as the tumor microenvironment undergo characteristic molecular changes, which are essential for the metastatic dissemination of tumor cells. In this review, we will discuss recent insights into pro-metastatic events occurring in tumor cells themselves and in the tumor stroma. Tumor cell-intrinsic alterations include the loss of cell polarity and alterations in cell-cell and cell-matrix Cell. Mol. Life Sci. 63 (2006) 449-468 1420-682X/06/040449-20 DOI 10.1007/s00018-005-5296-8 © Birkhäuser Verlag, Basel, 2006 adhesion as well as deregulated receptor kinase signaling, which together support detachment, migration and invasion of tumor cells. On the other hand, the tumor stroma, including endothelial cells, fibroblasts and cells of the immune system, is engaged in an active molecular crosstalk within the tumor microenvironment. Subsequent activation of blood vessel and lymph vessel angiogenesis together with inflammatory and immune-suppressive responses further promotes cancer cell migration and invasion, as well as initiation of the metastatic process.

show abstract

“…In previous studies when the area of the region of interest was adjusted to 1 mm 2 , microvessel counts have ranged from 31 (Takahashi et al, 1997) to 181 (Bossi et al, 1995), falling within 100 in most reports (Takahashi et al, 1995;Tokunaga et al, 1999;Tomisaki et al, 1996) for colonic carcinoma and 66 (Bossi et al, 1995) to 89 (Fox et al, 1998) for normal mucosa. This profound difference is attributable at least in part to the selection of the region of interest (invasive edge or inside tumor) in colonic carcinoma.…”

Section: Figurementioning

confidence: 99%

Microvessel Morphology and Vascular Endothelial Growth Factor Expression in Human Colonic Carcinoma With or Without Metastasis

Tsuji

Sasaki

Tanaka

et al. 2002

Laboratory Investigation

View full text Add to dashboard Cite

SUMMARY:We quantified microvessel morphology and vascular endothelial growth factor (VEGF) expression in human colonic carcinoma with or without metastasis. The cancerous growth and the noncancerous section of surgical specimens from 36 patients with colorectal carcinoma (14 without metastasis and 22 with metastasis) were studied. Tissue slices immunostained with CD34 were processed for microvessel counts (per mm 2 ), the mean diameter of microvessels ( m), and the mean spatial direction of microvessels (degree), defined by the angle between the longitudinal axis of microvessels and the direction perpendicular to the surface of the mucosa. Tissue slices immunostained with anti-VEGF antibody were processed for total epithelial cell counts (per mm 2 ), VEGF-positive cell counts (per mm 2 ), and VEGF-positive ratio (%). Carcinoma without metastasis had significantly larger microvessel counts (213 Ϯ 77, p Ͻ 0.01), larger microvessel diameter (7.99 Ϯ 1.77, p Ͻ 0.05), and larger spatial direction (47.2 Ϯ 8.3, p Ͻ 0.01) than normal tissue (144 Ϯ 49 for microvessel counts; 7.03 Ϯ 0.90 for microvessel diameter; 39.5 Ϯ 6.6 for spatial direction). Compared with carcinoma without metastasis, carcinoma with metastasis had a significantly larger microvessel diameter (9.75 Ϯ 2.65, p Ͻ 0.03) and lower microvessel counts (180 Ϯ 92, p ϭ 0.51). Carcinoma without metastasis had a significantly larger VEGF-positive cell count (1276 Ϯ 805, p Ͻ 0.05) and larger VEGF-positive ratio (53.6 Ϯ 39.3, p Ͻ 0.05) than normal tissue (571 Ϯ 553 for VEGF-positive cell counts; 24.6 Ϯ 23.2 for VEGF-positive ratio). Carcinoma with metastasis had a significantly lower total cell count (1443 Ϯ 237, p Ͻ 0.001) and lower VEGF-positive cell count (716 Ϯ 463, p Ͻ 0.05) than carcinoma without metastasis. With tumor progression, microvessel diameter significantly increased and microvessel counts decreased, which can be in part explained by VEGF expression. The microvessel diameter seems to be the dominant parameter responsible for cancer cell intravasation as the first step of metastasis. (Lab Invest 2002, 82:555-562).

show abstract

Thrombospondin 2 expression is correlated with inhibition of angiogenesis and metastasis of colon cancer

Cited by 102 publications

References 38 publications

Expression of Thrombospondin-1 in Resected Colorectal Liver Metastases Predicts Poor Prognosis

Expression of Thrombospondin-1 in Resected Colorectal Liver Metastases Predicts Poor Prognosis

Metastasis: cell-autonomous mechanisms versus contributions by the tumor microenvironment

Microvessel Morphology and Vascular Endothelial Growth Factor Expression in Human Colonic Carcinoma With or Without Metastasis

Contact Info

Product

Resources

About