Thrombospondin-1 expression as a prognostic predictor of pancreatic ductal carcinoma

Tobita, Kosuke; Kijima, Hiroshi; Dowaki, Shoichi; Oida, Yasuhisa; Kashiwagi, Hirokazu; Ishii, Masanori; Sugio, Yoshinori; Sekka, Takafumi; Ohtani, Yasuo; Tanaka, Makiko; Inokuchi, Sadaki; Makuuchi, Hiroyasu

doi:10.3892/ijo.21.6.1189

Cited by 34 publications

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“…The rate of stromal TSP1 expression was significantly higher in MI-IPMC and IC-IPMC than in noninvasive IPMC (P = 0.035, 0.005, Table 1), but there was no significant difference between MI-IPMC and IC-IPMC. Three cases (25.0%) of MI-IPMC and seven cases (63.6%) of IC-IPMC were diffusely positive, with more than 50% of the cancer stroma positive for TSP1, a similar level compared with conventional invasive ductal carcinoma of the pancreas (data not shown) (22). Furthermore, patients in the strongly positive group with more than 30% of the cancer stroma positive for TSP1 showed a significantly poorer prognosis compared to that of patients in the negative-weakly positive group (P = 0.008, log-rank test, Fig.…”

Section: Association Between Stromal Tsp1 Expression and The Malignanmentioning

confidence: 66%

“…Several investigators demonstrated that TSP1 may play an important role in tumor cell adhesion and invasion by regulating the plasminogen/plasmin system (3,4,6,16,18). Previously, we reported that TSP1 plays important roles in cancer cell growth and the metastasis of human pancreatic cancer, and that stromal TSP1 immnoreactivity is a good prognostic indicator for patients with pancreatic cancer (22). In the present study, we examined stromal TSP1 expression as a prognostic indicator and a new marker of stromal invasiveness in IPMN.…”

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confidence: 99%

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Stromal thrombospondin-1 expression is a prognostic indicator and a new marker of invasiveness in intraductal papillary-mucinous neoplasm of the pancreas

et al. 2010

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The invasion of intraductal papillary-mucinous neoplasm (IPMN) is sometimes difficult to diagnose using only ordinary hematoxylin-eosin sections. The aim of this study was to evaluate the invasion of IPMN more precisely using thrombospondin-1 (TSP1) immunohistochemistry as a useful adjunct to morphological examination. Eighty patients that underwent primary resection for pancreatic IPMNs were retrospectively analyzed. The 80 IPMNs were studied for the expression of TSP1, MUC1-CORE, MUC2, and MUC5AC. The cases were evaluated for dysplasia, the presence of invasion, hisological subtypes, and survival. The 80 IPMNs were classified into 29 intraductal papillary-mucinous adenomas (IPMAs), 10 borderline IPMNs, 18 noninvasive intraductal papillary-mucinous carcinomas (IPMCs), and 23 invasive IPMCs according to the WHO classification. Invasive IPMCs were further divided into 12 minimally invasive IPMCs (MI-IPMCs) and 11 invasive carcinomas originating from IPMCs (IC-IPMCs) according to the Japan Pancreatic Society classification. The rate of strongly positive cases with more than 30% of the cancer stroma area expressing TSP1 was significantly higher in MI-IPMC and IC-IPMC than in noninvasive IPMC (P = 0.035, 0.005). Furthermore, patients in the strongly positive group had a significantly poorer prognosis compared to patients in the negative-weakly positive group (P = 0.008, log-rank test). Of the 80 tumors, 22 were classified into gastric-, 45 into intestinal-, 7 into pancreatobiliary-, and 6 into oncocytic-type IPMNs according to criteria described previously. The cases with a strongly positive expression of TSP1 were frequently detected in the pancreatobiliary and oncocytic types (P = 0.001). In conclusion, stromal TSP1 expression is a prognostic indicator and a new marker of invasiveness in IPMN.Intraductal papillary-mucinous neoplasms of the pancreas (IPMNs) are a well-characterized group of intraductal, mucin-producing, cystic neoplasms of the pancreas with a clear malignant potential (1, 2). A half of surgically resected IPMNs are intraductal papillary-mucinous adenoma (IPMA) or borderline IPMN even under current international criteria (21), and it is still unclear when they change to noninvasive intraductal papillary-mucinous carcinoma (IPMC), how long IPMC retains a status of "carcinoma in situ", and when IPMC achieves invasiveness. Particularly, invasive carcinoma originating from intraductal papillary-mucinous carcinoma (IC-IPMC) showed similar malignant behavior compared with conventional invasive ductal carcinoma both clinically and histologically (15). Minimally invasive IPMC (MI-IPMC) has been categorized within the classification of pancreatic carcinoma used by

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Section: Association Between Stromal Tsp1 Expression and The Malignanmentioning

confidence: 66%

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confidence: 99%

Stromal thrombospondin-1 expression is a prognostic indicator and a new marker of invasiveness in intraductal papillary-mucinous neoplasm of the pancreas

et al. 2010

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“…For example, TSP-1 is constitutively expressed at a high level in fast-growing aggressive MDA-MB-231 human breast cancer cells (Uray et al 2004). However, TSP-1 may also have context-and tissue-dependent roles, and may stimulate wound healing, cell proliferation, and adhesion of some but not all human tumor cells (Incardona et al 1995, DiPietro et al 1996, Wang et al 1996a,b, Patel et al 1997, Tobita et al 2002, Wang-Rodriguez et al 2003, Poon et al 2004, Fontana et al 2005.…”

Section: Introductionmentioning

confidence: 99%

Regulation of thrombospondin-1 by natural and synthetic progestins in human breast cancer cells

Hyder¹,

Liang²,

Wu³

et al. 2009

Endocrine-Related Cancer

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Our recent studies show that progestins induce vascular endothelial growth factor (VEGF) in breast cancer cells that express mutant p53 protein. Here, we show that natural and synthetic progestins also induce thrombospondin-1 (TSP-1) mRNA and protein in T47-D and BT-474 breast cancer cells. Antiprogestin RU-486 inhibits the induction of VEGF and TSP-1 by progestins, suggesting that this effect of progestin is mediated by the progesterone receptor (PR). Actinomycin-D, but not puromycin, also blocks progestin-dependent induction of TSP-1. A putative progestin-response element was identified in the human TSP-1 promoter, which is consistent with the hypothesis that a progestin-PR complex might directly regulate transcription of the TSP-1 gene in human cells. Conditioned medium from progestin-treated breast cancer cells stimulates endothelial cell proliferation in the absence though not in the presence of antibody to TSP-1, indicating that TSP-1 secreted by breast cancer cells could be pro-angiogenic. Since tumor cell-derived TSP-1 has the potential to promote angiogenesis in the tumor microenvironment, it could be a potential target for breast cancer therapy.

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“…TSP-1 dictates the composition of these multi-protein complexes through specific interactions with growth factors, cytokines, other matrix components and membrane proteins [12]. The relationship between overexpression of TSP-1 in tumor tissues and their favorable prognosis is still controversial [13,14]. In many aspects, the gene expression profiles of thyroid malignancies and thyroid-derived fibroblasts are much alike.…”

Section: Discussionmentioning

confidence: 99%

Thrombospondin 1 mRNA as a Candidate for a Marker to Detect Thyroid-derived Fibroblasts in Fine Needle Aspiration Biopsy of the Thyroid

et al. 2006

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Abstract. Possible interference of fibroblasts is suggested in aspiration biopsy nucleic acid diagnosis (ABND). However, detection of fibroblasts in the aspirates is difficult, because the gene expression profiles of thyroid malignancies and fibroblasts are much alike in many aspects. To identify a specific marker for thyroid-derived fibroblasts, the data of the serial analysis of gene expression (SAGE) were compared to screen differentially expressed genes between fibroblasts and thyroid normal and tumor tissues. In the SAGE data, 5 genes were identified to be differentially expressed. Among these, thrombospondin 1 (TSP-1, THBS1) mRNA was the most differentially expressed. Further, the overexpression of TSP-1 mRNA in fibroblasts was confirmed by real-time RT-PCR analysis using 73 thyroid normal and tumor tissues and 7 cultures of thyroid-derived fibroblasts. These results suggest that TSP-1 mRNA is a possible marker for contamination of thyroid-derived fibroblasts.

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Thrombospondin-1 expression as a prognostic predictor of pancreatic ductal carcinoma

Cited by 34 publications

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Stromal thrombospondin-1 expression is a prognostic indicator and a new marker of invasiveness in intraductal papillary-mucinous neoplasm of the pancreas

Stromal thrombospondin-1 expression is a prognostic indicator and a new marker of invasiveness in intraductal papillary-mucinous neoplasm of the pancreas

Regulation of thrombospondin-1 by natural and synthetic progestins in human breast cancer cells

Thrombospondin 1 mRNA as a Candidate for a Marker to Detect Thyroid-derived Fibroblasts in Fine Needle Aspiration Biopsy of the Thyroid

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