Antisense-mediated reduction in thrombospondin reverses the malignant phenotype of a human squamous carcinoma.

Castle, Valerie P.; Varani, James; Fligiel, Susan; Prochownik, Edward V.; Dixit, Vishva M.

doi:10.1172/jci115212

Cited by 74 publications

(43 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…17,20,21 In contrast, suppression of TSP-1 expression by antisense TSP-1 cDNA suppressed the metastatic activity of the squamous carcinoma cell line. 22 Intravenous injection of TSP-1 into mice enhanced lung tumor colony formation by 2-to 3-fold. 23 These observations suggest that the overall effect of TSP-1 on tumor progression varies with tumor type.…”

Section: Discussionmentioning

confidence: 99%

Antisense‐mediated reduction in thrombospondin‐1 expression reduces cell motility in malignant glioma cells

et al. 2001

View full text Add to dashboard Cite

Thrombospondin-1 (TSP-1) is a multifunctional matrix protein implicated in cancer cell adhesion, migration, invasion, inhibition of angiogenesis and activation of latent transforming growth factor-␤. The involvement of TSP-1 in the motility of malignant glioma cells was investigated by transfection of TSP-1 complementary deoxyribonucleic acid (cDNA) sense and antisense expression vectors into the glioblastoma cell line T98G-G7 that secretes high amounts of TSP-1. TSP-1 production in the 3 antisense cDNA-transfected clones was significantly reduced to 51%, 43% and 47% compared to the host T98G-G7 cells. Motility of the 3 clones was evaluated by invasion assay and compared to the motility of host T98G-G7 cells and 2 sense-transfected clones. Migration of cells was significantly reduced in the 3 antisensetransfected clones with reduced TSP-1 production to 56%, 61% and 43% compared to the host T98G-G7 cells. The host T98G-G7 and another TSP-1-secreting A172 and YMG5 glioblastoma cells were also treated with a synthetic peptide, WSHWSPWSSCSVTCG, which includes 3 consecutive sequences of the adhesion sites in the TSP-1 molecule and with a control peptide. The synthetic peptide significantly inhibited the migration of T98G-G7 and A172 cells in a doserelated manner. Maximum inhibition of migration was achieved by 100 g/ml of the peptide and the reduction of cell motility compared to untreated cells was 34.6 % and 53.9 %, respectively. On the other hand, the inhibition of migration by the peptide was minimal in YMG5 cells, which secretes a smaller amount of TSP-1 than T98G-G7 and A172 cells. These results suggest that TSP-1 secreted by malignant glioma cells is involved in the motility of glioma cells. © 2001 Wiley-Liss, Inc. Key words: thrombospondin-1; glioma; glioblastoma; cell motility; invasionThrombospondin-1 (TSP-1) is a multifunctional matrix protein implicated in cancer cell adhesion, migration, invasion, inhibition of angiogenesis and activation of latent transforming growth factor-␤ (TGF-␤). 1,2 TSP-1 is a member of a family of structurally related proteins encoded by different genes, which includes 4 recently identified members designated TSP-2, TSP-3, TSP-4 and TSP-5/cartilage oligomeric matrix protein. 3 TSP-1 and TSP-2 have similar overall structures, which differ from those of TSP-3, TSP-4 and TSP-5. 3 TSP-1 is secreted by platelets and synthesized by many cell types, including endothelial and tumor cells. 1,2 TSP-1 consists of multiple domains, including an amino-terminal heparin-binding domain, a procollagen-like domain, 3 type I (properdin-like) repeats, 3 type II (epidermal growth factor-like) repeats, 7 type III (calcium-binding) repeats and a carboxy-terminal cellbinding domain that lacks homology to other proteins. Eleven sites for adhesion have been identified. 1 A potential role for TSP-1 in cancer is suggested by its regulated expression in many normal and tumor cells and by its ability to modulate the adhesion and motility of many types of tumor cells in vitro. 4 Adhesion molecules are potentia...

show abstract

Section: Discussionmentioning

confidence: 99%

Antisense‐mediated reduction in thrombospondin‐1 expression reduces cell motility in malignant glioma cells

et al. 2001

View full text Add to dashboard Cite

show abstract

“…However, the involvement of TSP-1 in tumor progression remains complex and controversial since both stimulatory (19,20) and inhibitory (21,22) effects in angiogenesis have been described and assigned to up-regulation of matrix-degrading enzymes and their inhibitors.…”

mentioning

confidence: 99%

Activating Transcription Factor-1-mediated Hepatocyte Growth Factor-induced Down-regulation of Thrombospondin-1 Expression Leads to Thyroid Cancer Cell Invasion

Ghoneim

Soula-Rothhut

Blanchevoye

et al. 2007

Journal of Biological Chemistry

View full text Add to dashboard Cite

Hepatocyte growth factor (HGF) plays a major role in the pathogenesis of a variety of human epithelial tumors including papillary carcinoma of the thyroid. Previous reports demonstrated that HGF, acting through the Met receptor, repressed thrombospondin-1 (TSP-1) expression. To study the mechanisms by which HGF down-regulated TSP-1 expression, we transiently transfected a panel of deleted human TSP-1 promoter reporter plasmids into papillary thyroid carcinoma cells. We identified a region between ؊1210 and ؊1123 bp relative to the transcription start site that is responsive to HGF treatment and harbors a cAMP-responsive element (CRE) at position ؊1199 (TGACGTCC). Overexpression of various members of the CRE-binding protein family identified activating transcription factor-1 (ATF-1) as the transcription factor responsible for HGF-induced repression of TSP-1 promoter activity. This inhibition was associated with a concomitant increase in the abundance of nuclear ATF-1 protein. Gel shift and antibody supershift studies indicated that ATF-1 was involved in DNA binding to the TSP-1-CRE site. Finally, we utilized small hairpin RNA to target ATF-1 and showed that these small interfering RNA constructs significantly inhibited ATF-1 expression at both the RNA and the protein level. ATF-1 knockdown prevented HGFinduced down-regulation of TSP-1 promoter activity and protein expression and also reduced HGF-dependent tumor cell invasion. Taken together, our results indicate that HGF-induced down-regulation of TSP-1 expression is mediated by the interaction of ATF-1 with the CRE binding site in the TSP-1 promoter and that this transcription factor plays a crucial role for tumor invasiveness in papillary carcinoma of the thyroid triggered by HGF.

show abstract

“…3 Thrombospondin-1 (TSP-1) has been reported to be down-regulated in cutaneous SCC, and the overexpression of TSP-1 in two stable transfected SCC cell lines inhibited tumor growth in vivo. 4 These results conflict with those of Castle et al, 5 who found that subcutaneous inoculation of athymic mice with human SCC cell lines transfected with TSP cDNA antisense expression vector reduced TSP production and inhibited tumor growth.…”

Section: Angiogenesis In Cutaneous Diseasementioning

confidence: 80%

Angiogenesis in cutaneous disease: Part II

Laquer

Hoang

Nguyen

et al. 2009

Journal of the American Academy of Dermatology

View full text Add to dashboard Cite

This review will discuss the role of angiogenesis in specific cutaneous diseases. Scientific evidence now points to the role of angiogenesis in tumor development and many other cutaneous disorders. Angiogenesis is a complex process that involves angiogenic growth factors and inhibitors, many of which could be a potential target for pharmacologic intervention. Antiangiogenic agents have recently been applied to dermatologic diseases with promising efficacy. ( J Am Acad Dermatol 2009;61:945-58.)Learning objectives: After completing this learning activity, participants should be able to recognize cutaneous diseases where angiogenesis is likely to be an important factor, recognize scenarios where angiogenic therapy may be useful in conjunction with traditional therapies, and be able to use angiogenicmediating agents in the treatment of dermatologic disease.

show abstract

Antisense-mediated reduction in thrombospondin reverses the malignant phenotype of a human squamous carcinoma.

Cited by 74 publications

References 24 publications

Antisense‐mediated reduction in thrombospondin‐1 expression reduces cell motility in malignant glioma cells

Antisense‐mediated reduction in thrombospondin‐1 expression reduces cell motility in malignant glioma cells

Activating Transcription Factor-1-mediated Hepatocyte Growth Factor-induced Down-regulation of Thrombospondin-1 Expression Leads to Thyroid Cancer Cell Invasion

Angiogenesis in cutaneous disease: Part II

Contact Info

Product

Resources

About