Lipopolysaccharide (LPS) enhances prostate cancer metastasis potentially through NF‐κB activation and recurrent dexamethasone administration fails to suppress it in vivo

Abstract

Background Previous studies have shown the effect of bacterial lipopolysaccharide (LPS) on enhanced cancer cells’ growth and metastasis. However, the effect of LPS on prostate cancer (PCa) cells metastasis has not been investigated in details. This study aimed to investigate the functional role of LPS on PCa cells metastasis and determine the effect of dexamethasone (DEX) on this event. Methods Two different PCa reporter cells lines (DU145‐NF‐κB‐Luc and MAT‐LyLu‐ NF‐κB‐Luc) were used to assess the direct effect of LPS on NF‐κB activation in PCa cells. Plasma collected from LPS‐stimulated human and rodent blood were used to check the indirect effect of LPS on NF‐κB activation in PCa cells. Trans‐well migration assay and two different orthotopic PCa animal models were used to investigate the effect of LPS on DU145 and MAT‐LyLu cells migration or metastasis in vitro and in vivo, respectively. In all the studies DEX was used with or without LPS stimulation. Results LPS and secretory factors present in plasma collected from LPS‐stimulated blood, significantly activated NF‐κB in DU145, and MAT‐LyLu cells and enhanced their migration in vitro. DEX significantly suppressed LPS‐mediated activation of cancer and blood cells and abrogated the direct and indirect pro‐migratory effect of LPS on PCa cells. Systemic administration of LPS activated NF‐κB in DU145 cells in vivo; however, failed to alter the metastatic properties of these cells. On the other hand, systemic administration of LPS to MAT‐LyLu tumor bearing animals significantly enhanced the incidence of metastasis without altering the overall growth of primary tumors. Unexpectedly, though DEX significantly suppressed MAT‐LyLu primary tumor weights, it aggravated metastasis of cancer cells in presence and absence of LPS. Moreover, consecutive DEX pre‐treatment enhanced experimental peritoneal metastasis of MAT‐LyLu cells. At the molecular level, LPS, and/or DEX induced overexpression of immunosuppressive molecules in MAT‐LyLu tumors. Conclusions Overall, our study has shown that LPS and/or LPS induced inflammation can increase PCa metastasis and immunosuppressive dose of DEX might further enhance cancer metastasis.

Escherichia coli, a common constituent of benign prostate hyperplasia‐associated microbiota induces inflammation and DNA damage in prostate epithelial cells

“…Inflammatory signaling involving nuclear factor‐κB (NF‐κB) 20‐22 and cyclooxygenase‐2 (COX2) 23,24 is also reported to be intricate in PC pathogenesis. Our earlier study has also reported that bacterial component lipopolysaccharide (LPS) can induce NF‐κB activation in PC cells and promote survival and/or metastasis of these cells 25,26 …”

Epigenetic induction of tumor stemness via the lipopolysaccharide-TET3-HOXB2 signaling axis in esophageal squamous cell carcinoma

“…A large number of studies have proved that LPS participated in stimulating the progression of several types of tumors, He and colleagues found that LPS promotes the migration of oral squamous cell carcinoma by activating the epithelial-mesenchymal transition signaling pathway [29]. Jain and colleagues confirmed that LPS promoted the distant metastasis of prostate cancer by activating NF-κB signaling pathway, and further accelerated the metastasis under the stimulation of dexamethasone [30]. In addition to the effects of LPS on migration and metastasis, some researchers have reported the effect of LPS on tumor proliferation.…”

Epigenetic induction of tumor stemness via the Lipopolysaccharide-TET3-HOXB2 signaling axis in esophageal squamous cell carcinoma

“…A large number of studies have proved that LPS participated in stimulating the progression of several types of tumors, He and colleagues found that LPS promotes the migration of oral squamous cell carcinoma by activating the epithelial-mesenchymal transition signaling pathway [30]. Jain and colleagues confirmed that LPS promoted the distant metastasis of prostate cancer by activating NF-κB signaling pathway, and further accelerated the metastasis under the stimulation of dexamethasone [31]. In addition to the effects of LPS on migration and metastasis, some researchers have reported the effect of LPS on tumor proliferation.…”