Expression, regulation and function of autotaxin in thyroid carcinomas

Kehlen, Astrid; Englert, Nadine C.; Seifert, Anja; Klonisch, Thomas; Dralle, Henning; Langner, Jürgen; Hoang‐Vu, Cuong

doi:10.1002/ijc.20022

Cited by 111 publications

(104 citation statements)

References 33 publications

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“…Each tumor was scored according to the pTNM classification (16 RNA isolation and cDNA synthesis. RNA isolation and reverse transcription have recently been described (9). Briefly, a first strand cDNA synthesis was performed according to the manufacturer's instructions using 500 ng total RNA, 50 pmol of random primer (Roche, Mannheim, Germany), and 0.5 μl (200 U/μl) Superscript™ II-RT (Invitrogen, Karlsruhe, Germany).…”

Section: Thyroid Tissues and The Ftc-238 Cell Linementioning

confidence: 99%

“…FTC-133 stable transfectants overexpressing a soluble ATX showed a higher lysoPLD activity, enhanced proliferation and an increased migratory activity. ATX also showed a paracrine stimulatory effect on the motility of other thyroid carcinoma cell lines (9). When expressed in FTC-133 or COS-1 cells, ATX was mainly found in the supernatant, whereas NPP1 was abundant in cell lysates (9,15).…”

Section: Introductionmentioning

confidence: 96%

“…ATX stimulates random and directed motility in a variety of tumor cell lines, including those from breast, renal and ONCOLOGY REPORTS 19: 1485-1491, 2008 The cellular localization of autotaxin impacts on its biological functions in human thyroid carcinoma cells thyroid carcinoma, melanoma and neuroblastoma (1,(9)(10)(11)(12). ATX augments the tumorigenic capacity and metastatic potential of ras-transformed cells and appears to act as an angiogenic factor (13,14).…”

Section: Introductionmentioning

confidence: 99%

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The cellular localization of autotaxin impacts on its biological functions in human thyroid carcinoma cells

Seifert

Klonisch²,

Wulfaenger³

et al. 2008

Oncol Rep

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Abstract. Autotaxin (ATX/NPP2) shows a nucleotide pyrophosphatase/phosphodiesterase and lysophospholipase D (lysoPLD) activity and is a member of a family of structurallyrelated mammalian ecto-nucleotide pyrophosphate/phosphodiesterases (E-NPP1-3). ATX is unique among E-NPP as it is secreted and not membrane-bound as are NPP1 and -3. The ATX gene activity is significantly higher in undifferentiated anaplastic (UTC) as compared to follicular (FTC) and papillary thyroid carcinomas (PTC) or goiter tissues. ATX also enhances the motility of thyroid tumor cells. We bioengineered stable transfectants of the human thyroid carcinoma cell line FTC-238 expressing either bioactively-secreted (sATX) or membrane-anchored ATX (mATX) to identify the biological functions of ATX which critically depend on the E-NPP member being secreted and provide insight into the effects of high local ATX concentrations and cellular responses. An increased cell motility was exclusively observed with FTC-238 sATX transfectants, whereas membraneanchored ATX appeared to impair motility. We identified IL-1ß as an upstream suppressor of ATX expression in FTC-238, ATX-mediated motility in FTC-238 and stable transfectants, with IL-1ß having the strongest motility-suppressive effect on FTC-238 sATX clones. sATX and mATX strongly increased the anchorage-independent colony formation of FTC-238 but the size and number of colonies formed in the soft agar were significantly smaller in FTC-238 mATX versus the FTC-238 sATX clones. The cancer-testis antigen BAGE was identified as a novel target gene of ATX in FTC-238. Transcript levels for BAGE were 6-fold higher in FTC-238 mATX versus sATX clones. Increased BAGE transcript levels were also detected in tissues of patients with UTC versus FTC, PTC or goiter tissues. In summary, enhanced tumor cell motility and tumorigenic capacity critically depended on sATX in thyroid carcinoma cells. Irrespective of its compartmentalization, the cancer-testis antigen BAGE was identified as a novel target gene of ATX in FTC-238 and a potential new tissue marker in UTC tissues, which we had previously shown to express high levels of ATX.

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Section: Thyroid Tissues and The Ftc-238 Cell Linementioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

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The cellular localization of autotaxin impacts on its biological functions in human thyroid carcinoma cells

Seifert

Klonisch²,

Wulfaenger³

et al. 2008

Oncol Rep

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“…23], thyroid carcinoma (where it correlates with the aggressive anaplastic variant of thyroid carcinoma compared with the less aggressive follicular thyroid carcinoma cell lines; ref. 24), and ovarian cancer (where astronomical levels of the enzymatic product of ATX are found in the malignant ascitic fluids; refs. 25 -28).…”

Section: Introductionmentioning

confidence: 99%

Identification of small-molecule inhibitors of autotaxin that inhibit melanoma cell migration and invasion

Saunders

Ouellette

Bandle

et al. 2008

Molecular Cancer Therapeutics

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Autotaxin (ATX) is a prometastatic enzyme initially isolated from the conditioned medium of human melanoma cells that stimulates a myriad of biological activities, including angiogenesis and the promotion of cell growth, survival, and differentiation through the production of lysophosphatidic acid (LPA). ATX increases the aggressiveness and invasiveness of transformed cells, and ATX levels directly correlate with tumor stage and grade in several human malignancies. To study the role of ATX in the pathogenesis of malignant melanoma, we developed antibodies and small-molecule inhibitors against recombinant human protein. Immunohistochemistry of paraffinembedded human tissue shows that ATX levels are markedly increased in human primary and metastatic melanoma relative to benign nevi. Chemical screens identified several small-molecule inhibitors with binding constants ranging from nanomolar to low micromolar. Cell migration and invasion assays with melanoma cell lines show that ATX markedly stimulates melanoma cell migration and invasion, an effect suppressed by ATX inhibitors. The migratory phenotype can be rescued by the addition of the enzymatic product of ATX, LPA, confirming that the observed inhibition is linked to suppression of LPA production by ATX. Chemical analogues of the inhibitors show structure-activity relationships important for ATX inhibition and indicate pathways for their optimization. These studies suggest that ATX is an approachable molecular target for the rational design of chemotherapeutic agents directed against malignant melanoma. [Mol Cancer Ther 2008;7(10):3352 -62]

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“…LPA is produced by enzymatic activity of either ATX or PLA 2 . ATX expression is growth factor dependent, and it has been shown to be up-regulated by bFGF, EGF and VEGF [97,98]. The peritoneal mesothelium constitutively produces PLA 2 , so translocated ovarian cells are constantly exposed to its presence [99].…”

Section: Lpamentioning

confidence: 99%

Toward an Integrative Analysis of the Tumor Microenvironment in Ovarian Epithelial Carcinoma

Serio

2011

Cancer Microenvironment

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Expression, regulation and function of autotaxin in thyroid carcinomas

Cited by 111 publications

References 33 publications

The cellular localization of autotaxin impacts on its biological functions in human thyroid carcinoma cells

The cellular localization of autotaxin impacts on its biological functions in human thyroid carcinoma cells

Identification of small-molecule inhibitors of autotaxin that inhibit melanoma cell migration and invasion

Toward an Integrative Analysis of the Tumor Microenvironment in Ovarian Epithelial Carcinoma

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