We have previously demonstrated that anti-CD44s H4C4 or liposomal-delivered STAT3 inhibitor FLLL32 sensitized pancreatic cancer cells to radiotherapy through the elimination or inhibition of cancer stem cells (CSCs) and that HAb18G/CD147 promoted STAT3-mediated pancreatic tumor development by forming a signaling complex with CD44s.
The findings implicate epithelial tension and matricellular fibrosis in the aggressiveness of SMAD4 mutant pancreatic tumors and highlight STAT3 and mechanics as key drivers of this phenotype.
Stat3, Il6st (encodes gp130), or Trp53 were disrupted, or a mutant form of P53 (P53R172H) or transgenic sgp130 were expressed, in mice that developed pancreatic tumors resulting from expression of activated KRAS (KrasG12D, KC mice).
In mice that were fed BITC (60 micromol/wk, five mice, 10 tumors per group), growth of BxPC-3 pancreatic tumor xenografts was suppressed compared with control mice (at 6 weeks, mean tumor volume of control vs BITC-treated mice = 334 vs 172 mm3, difference =162 mm3, 95% confidence interval = 118 to 204 mm3; P = .008) and tumors had increased apoptosis and reduced STAT-3 protein expression.
Mesothelin-induced pancreatic cancer cell proliferation involves alteration of cyclin E via activation of signal transducer and activator of transcription protein 3.
RNA interference-mediated signal transducers and activators of transcription 3 gene silencing inhibits invasion and metastasis of human pancreatic cancer cells.
Targeting heat shock protein 90 in pancreatic cancer impairs insulin-like growth factor-I receptor signaling, disrupts an interleukin-6/signal-transducer and activator of transcription 3/hypoxia-inducible factor-1alpha autocrine loop, and reduces orthotopic tumor growth.