Mesenchymal stem cells‐derived IL‐6 promotes invasion and metastasis of oral squamous cell carcinoma via JAK‐STAT3 signalling

Abstract

ObjectivesOral squamous cell carcinoma (OSCC) is often diagnosed with cervical lymph node metastasis. Mesenchymal stem cells (MSCs) and interleukin‐6 (IL‐6) signalling are considered to play important roles in promoting tumour malignancy. The detailed biological interaction of MSCs and IL‐6 and the subsequent effect on OSCC metastasis remain largely unclear. This study aimed to determine the effects and molecular mechanism of MSCs‐derived IL‐6 on tumour invasion and metastasis.Subjects and MethodsThe effects of MSC‐derived IL‐6 and tocilizumab on the proliferation, mobility, and epithelial‐mesenchymal transition (EMT) of OSCC cells and potential pathways were detected in vitro. In addition, a murine xenograft model was generated to verify the biological mechanism in vivo.ResultsThe results showed that the expression of MSCs and EMT‐related signals was increased in poorly differentiated OSCC tissues. MSCs released a higher level of IL‐6 and promoted the proliferation, invasion, and metastasis of OSCC cells and solid neoplasms, which were activated by the downstream molecules JAK and STAT3.ConclusionsThe results indicated that MSCs‐derived IL‐6‐promoted tumour invasion and metastasis via JAK–STAT3 signalling. Blockade of this pathway by tocilizumab may be a potential treatment to improve the prognosis and survival rate of patients with OSCC.

The potential mechanism of WT1‐associated protein‐induced N‐6‐methyladenosine modification of colony‐stimulating factor 2 in the progression of oral squamous cell carcinoma by JAK/STAT3 pathway regulation

“…Zhang et al [27] found that OSCC oncogenes activate the JAK/STAT3 pathway by promoting JAK2 and STAT3 phosphorylation, which ultimately induces the metastasis of OSCC cells [27]. As reported by Liu et al [28], the activation of the JAK/STAT3 signaling pathway facilitated OSCC oncogenicity and metastasis. Alain et al…”

About a Possible Impact of Endodontic Infections by Fusobacterium nucleatum or Porphyromonas gingivalis on Oral Carcinogenesis: A Literature Overview

“…STATs are ignited by the Janus-associated kinases (JAKs) [6]. In bacterial-infected and inflamed oral cavity, JAKs can be triggered by F. nucleatum and P. gingivalis [43,46] or upon the binding of IL-1β, IL-6, IL-8, TNF-α, EGF, or TGF-β to their membrane receptors [81][82][83][84][85][86][87]. In this context, it must be underlined that, while they directly activate the JAKs, F. nucleatum and P. gingivalis stimulate OSCC cells to produce the abovementioned JAK-activating cytokines [14][15][16][17][18][19][20][21][22][23][24].…”

“…Among STAT family members, STAT3 is over-activated in OSCCs, where it strengthens the viability and promotes the proliferation of OSCC cells [82,83,86,90].…”