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Deciphering the oncogenic influence of Pasteurella multocida: Implications of matrix metalloproteinase activation

Jyotsna Nambiar1, Meera Venugopal1, Sanu Korumadathil Shaji2

  • 1Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Clappana P O, Kollam, Kerala, 690525, India.

Heliyon
|March 3, 2025
PubMed

Insights

Pathogenic bacteria like Pasteurella multocida promote cancer cell proliferation by interfering with host cell signaling. This study shows bacterial components induce matrix metalloproteinases and survival pathways, increasing cancer cell migration and invasion.

Area of Science:

  • Microbiology and Cancer Biology
  • Investigates the intricate interplay between bacterial pathogens and host cellular mechanisms in cancer progression.

Background:

  • Pathogenic bacteria, such as Pasteurella multocida, can exploit host cells by disrupting signaling pathways.
  • Pasteurella multocida toxin (PMT) is a potent mitogen with tumor-promoting properties, highlighting the bacterium's potential role in cancer.
  • Understanding how bacteria influence cancer cell behavior is crucial for developing effective therapeutic strategies.

Purpose of the Study:

  • To examine the mitogenic potential of Pasteurella multocida components on fibrosarcoma cells (HT1080).
  • To investigate the effects of P. multocida on matrix metalloproteinase (MMP) activity, cell survival pathways, and cancer cell migration/invasion.
  • To evaluate the impact of P. multocida on plumbagin-induced cell death in cancer cells.

Main Methods:

  • Assessed the mitogenic effects of P. multocida cell lysate and culture supernatant on HT1080 fibrosarcoma cells.
  • Measured Matrix metalloproteinase-2 (MMP-2) and Matrix metalloproteinase-9 (MMP-9) activity, along with Tissue Inhibitor of Metalloproteinases (TIMP-2) and reversion inducing cysteine rich protein with kazal motifs (RECK) levels.
  • Analyzed the activation of p44/42MAPK and Akt signaling pathways and evaluated cell migration and invasion assays.
  • Investigated the influence of P. multocida components on plumbagin-induced cell death.

Main Results:

  • P. multocida cell lysate and supernatant significantly induced MMP-2 and MMP-9 activity.
  • Downregulation of endogenous MMP inhibitors (TIMP-2 and RECK) was observed.
  • Mitogenic and cell survival pathways (p44/42MAPK, Akt) were induced, leading to increased HT1080 cell migration and invasion.
  • Bacterial components reduced plumbagin-induced cancer cell death, indicating a pro-proliferative effect.

Conclusions:

  • Pasteurella multocida components promote cancer cell proliferation by enhancing MMP activity and survival pathways.
  • Bacterial infections can worsen existing cancers by increasing cell migration, invasion, and resistance to cell death.
  • Novel therapeutic approaches are needed to address the role of bacterial infections in cancer progression.
Keywords:
CancerInfectionsMMPP. multocida

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