Expression of activated and latent signal transducer and activator of transcription 3 in 303 non-small cell lung carcinomas and 44 malignant mesotheliomas: Possible role for chemotherapeutic intervention

Rosane De Oliveira Duarte Achcar, Philip T. Cagle, Jaishree Jagirdar

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23 Citations (Scopus)

Abstract

Context. - Signal transducer and activator of transcription 3 (STAT3) is constitutively activated in diverse human cancers and plays a critical role in tumor cell survival, proliferation, migration, invasion, angiogenesis, and inhibition of apoptosis. The phosphorylated active form of STAT3 (pSTAT3) mediates its effects via nuclear transcriptional activity. However, it was recently observed that the non-phosphorylated, cytoplasmic, inactive form of STAT3 is involved in cell motility and consequently tumor invasion. It appears that, although STAT3 is not absolutely required for tumor formation, tumors that develop in the presence of STAT3 become dependent on its expression for their survival, making it a potential therapeutic target. Objective. - To investigate the possible utility of STAT3 as a future therapeutic target in non-small cell lung carcinoma (NSCLC) and malignant mesothelioma (MM). Design. - Immunohistochemical expression of MIB-1, STAT3, and pSTAT3 was assessed in 303 NSCLC and 44 MM archival cases. Results. - A more conspicuous expression of inactive STAT3 (91.44% in NSCLC and 79.5% in MM cases) was present compared with the nuclear activated form pSTAT3 (60.53% in NSCLC and 61.4% in MM cases). MIB-1 did not correlate with the expression of STAT3 or pSTAT3. Conclusions. - The strong expression of cytoplasmic inactive STAT3 in NSCLC and MM cases implies a major role for STAT3 in tumor motility, invasion, and metastasis via a nontranscriptional pathway. We conclude that STAT3 and pSTAT3 are up-regulated in a high percentage of NSCLCs and MMs, regardless of tumor type, age, sex, smoking status, stage and grade of tumor, or survival, providing a basis for therapeutic intervention.

Original languageEnglish (US)
Pages (from-to)1350-1360
Number of pages11
JournalArchives of Pathology and Laboratory Medicine
Volume131
Issue number9
StatePublished - Sep 2007

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STAT3 Transcription Factor
Non-Small Cell Lung Carcinoma
Neoplasms
Malignant Mesothelioma
Cell Movement
Cell Survival
Therapeutics

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Medical Laboratory Technology
  • Medicine(all)

Cite this

Expression of activated and latent signal transducer and activator of transcription 3 in 303 non-small cell lung carcinomas and 44 malignant mesotheliomas : Possible role for chemotherapeutic intervention. / Achcar, Rosane De Oliveira Duarte; Cagle, Philip T.; Jagirdar, Jaishree.

In: Archives of Pathology and Laboratory Medicine, Vol. 131, No. 9, 09.2007, p. 1350-1360.

Research output: Contribution to journalArticle

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abstract = "Context. - Signal transducer and activator of transcription 3 (STAT3) is constitutively activated in diverse human cancers and plays a critical role in tumor cell survival, proliferation, migration, invasion, angiogenesis, and inhibition of apoptosis. The phosphorylated active form of STAT3 (pSTAT3) mediates its effects via nuclear transcriptional activity. However, it was recently observed that the non-phosphorylated, cytoplasmic, inactive form of STAT3 is involved in cell motility and consequently tumor invasion. It appears that, although STAT3 is not absolutely required for tumor formation, tumors that develop in the presence of STAT3 become dependent on its expression for their survival, making it a potential therapeutic target. Objective. - To investigate the possible utility of STAT3 as a future therapeutic target in non-small cell lung carcinoma (NSCLC) and malignant mesothelioma (MM). Design. - Immunohistochemical expression of MIB-1, STAT3, and pSTAT3 was assessed in 303 NSCLC and 44 MM archival cases. Results. - A more conspicuous expression of inactive STAT3 (91.44{\%} in NSCLC and 79.5{\%} in MM cases) was present compared with the nuclear activated form pSTAT3 (60.53{\%} in NSCLC and 61.4{\%} in MM cases). MIB-1 did not correlate with the expression of STAT3 or pSTAT3. Conclusions. - The strong expression of cytoplasmic inactive STAT3 in NSCLC and MM cases implies a major role for STAT3 in tumor motility, invasion, and metastasis via a nontranscriptional pathway. We conclude that STAT3 and pSTAT3 are up-regulated in a high percentage of NSCLCs and MMs, regardless of tumor type, age, sex, smoking status, stage and grade of tumor, or survival, providing a basis for therapeutic intervention.",
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