Papillary carcinoma of the thyroid: High expression of COX-2 and low expression of KAI-1/CD82 are associated with increased tumor invasiveness

Stefania Scarpino, Enrico Duranti, Simona Giglio, Arianna Di Napoli, Dino Galafate, Donatella Del Bufalo, Marianna Desideri, Fabio Socciarelli, Antonella Stoppacciaro, Luigi Ruco

Research output: Contribution to journalArticle

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Abstract

Background: We have previously demonstrated that expression of COX-2 is upregulated by hepatocyte growth factor in thyroid papillary carcinoma (TPC) cells and is associated with increased invasiveness of tumor cells. COX-2 upregulation was associated with downregulation of KAI-1/CD82, a metastasis suppressor molecule that has been associated with the metastatic potential of several solid tumors. In the present study, we have investigated the possibility that downregulation of KAI-1/CD82 may contribute to the invasiveness of papillary carcinoma cells. Methods: Expression of KAI-1/CD82 and its relation to COX-2 levels were investigated in 6 primary cultures of TPC, in 2 tumor cell lines (TPC-1 and K1), and in 55 tumor samples of TPC. The biological role of KAI-1/CD82 in regulating tumor invasiveness was investigated in TPC cell lines and primary cultures transfected with a pCDNA3.1/Hygro.KAI-1; transfected cells were tested in functional studies of cell migration and invasiveness. Finally, the role of KAI-1/CD82 in influencing TPC metastasis was investigated in vivo using nu/nu mice injected with K1-transfected cells. Results: We provide evidence that COX-2 and KAI-1/CD82 are inversely regulated in TPC primary cultures and in TPC-1 tumor cells. In fact, inhibition of COX-2 with NS398 is associated with a 2-9-fold upregulation of KAI-1/CD82 RNA. Moreover, a possible relation between COX-2 and KAI-1/CD82 was confirmed by the presence of a statistically significant inverse correlation in the expression of the two genes in 55 tumor samples of TPC (r=-0.513; p=0.001). In 36 of 55 cases, tumor areas contained lower levels of KAI-1/CD82 RNA as compared with the corresponding normal tissue. Low expression of KAI-1/CD82 RNA in the tumor area was associated with extrathyroid extension of the disease in 16 of 19 cases (p

Original languageEnglish
Pages (from-to)1127-1137
Number of pages11
JournalThyroid
Volume23
Issue number9
DOIs
Publication statusPublished - Sep 1 2013

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Neoplasms
RNA
Up-Regulation
Down-Regulation
Neoplasm Metastasis
Papillary Thyroid cancer
Hepatocyte Growth Factor
Papillary Carcinoma
Tumor Cell Line
Cell Movement
Gene Expression
Cell Line

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Medicine(all)

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Papillary carcinoma of the thyroid : High expression of COX-2 and low expression of KAI-1/CD82 are associated with increased tumor invasiveness. / Scarpino, Stefania; Duranti, Enrico; Giglio, Simona; Di Napoli, Arianna; Galafate, Dino; Del Bufalo, Donatella; Desideri, Marianna; Socciarelli, Fabio; Stoppacciaro, Antonella; Ruco, Luigi.

In: Thyroid, Vol. 23, No. 9, 01.09.2013, p. 1127-1137.

Research output: Contribution to journalArticle

Scarpino, S, Duranti, E, Giglio, S, Di Napoli, A, Galafate, D, Del Bufalo, D, Desideri, M, Socciarelli, F, Stoppacciaro, A & Ruco, L 2013, 'Papillary carcinoma of the thyroid: High expression of COX-2 and low expression of KAI-1/CD82 are associated with increased tumor invasiveness', Thyroid, vol. 23, no. 9, pp. 1127-1137. https://doi.org/10.1089/thy.2011.0421
Scarpino, Stefania ; Duranti, Enrico ; Giglio, Simona ; Di Napoli, Arianna ; Galafate, Dino ; Del Bufalo, Donatella ; Desideri, Marianna ; Socciarelli, Fabio ; Stoppacciaro, Antonella ; Ruco, Luigi. / Papillary carcinoma of the thyroid : High expression of COX-2 and low expression of KAI-1/CD82 are associated with increased tumor invasiveness. In: Thyroid. 2013 ; Vol. 23, No. 9. pp. 1127-1137.
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abstract = "Background: We have previously demonstrated that expression of COX-2 is upregulated by hepatocyte growth factor in thyroid papillary carcinoma (TPC) cells and is associated with increased invasiveness of tumor cells. COX-2 upregulation was associated with downregulation of KAI-1/CD82, a metastasis suppressor molecule that has been associated with the metastatic potential of several solid tumors. In the present study, we have investigated the possibility that downregulation of KAI-1/CD82 may contribute to the invasiveness of papillary carcinoma cells. Methods: Expression of KAI-1/CD82 and its relation to COX-2 levels were investigated in 6 primary cultures of TPC, in 2 tumor cell lines (TPC-1 and K1), and in 55 tumor samples of TPC. The biological role of KAI-1/CD82 in regulating tumor invasiveness was investigated in TPC cell lines and primary cultures transfected with a pCDNA3.1/Hygro.KAI-1; transfected cells were tested in functional studies of cell migration and invasiveness. Finally, the role of KAI-1/CD82 in influencing TPC metastasis was investigated in vivo using nu/nu mice injected with K1-transfected cells. Results: We provide evidence that COX-2 and KAI-1/CD82 are inversely regulated in TPC primary cultures and in TPC-1 tumor cells. In fact, inhibition of COX-2 with NS398 is associated with a 2-9-fold upregulation of KAI-1/CD82 RNA. Moreover, a possible relation between COX-2 and KAI-1/CD82 was confirmed by the presence of a statistically significant inverse correlation in the expression of the two genes in 55 tumor samples of TPC (r=-0.513; p=0.001). In 36 of 55 cases, tumor areas contained lower levels of KAI-1/CD82 RNA as compared with the corresponding normal tissue. Low expression of KAI-1/CD82 RNA in the tumor area was associated with extrathyroid extension of the disease in 16 of 19 cases (p",
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AU - Giglio, Simona

AU - Di Napoli, Arianna

AU - Galafate, Dino

AU - Del Bufalo, Donatella

AU - Desideri, Marianna

AU - Socciarelli, Fabio

AU - Stoppacciaro, Antonella

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