Stimulation of cell surface plasminogen activation by membrane-bound melanotransferrin: a key phenomenon for cell

Jonathan Michaud-Levesque1, Michel Demeule, Richard Béliveau

  • 1Laboratoire de Médecine Moléculaire, Service d'Hémato-Oncologie, Hôpital Ste-Justine-Université du Québec à Montréal (UQAM), C.P. 8888, Succursale Centre-ville, Montréal, Québec, Canada H3C 3P8.

Insights

Membrane-bound melanotransferrin (mMTf) acts as a cell surface receptor, enhancing plasminogen binding and activation. This process significantly increases cell migration and invasion, highlighting mMTf

Area of Science:

  • Cell Biology
  • Biochemistry
  • Cancer Research

Background:

  • Cell surface plasminogen activation is vital for cell migration and invasion.
  • Melanotransferrin (MTf), also known as human melanoma antigen p97, is implicated in cellular processes.

Purpose of the Study:

  • To investigate the role of membrane-bound melanotransferrin (mMTf) in cell surface plasminogen binding and activation.
  • To determine the impact of mMTf on cell migration, motility, and invasion.

Main Methods:

  • Utilized Chinese Hamster Ovary (CHO) cells transfected with MTf cDNA and SK-MeL-28 melanoma cells.
  • Assessed plasminogen binding and activation on cell surfaces.
  • Evaluated cell motility, migration, and invasion rates.
  • Employed monoclonal antibody L235 and soluble MTf (sMTf) to inhibit mMTf function.

Main Results:

  • mMTf expression in CHO cells increased cell surface plasminogen binding approximately 2-fold.
  • mMTf expression stimulated cell surface plasminogen activation by about 2.5-fold.
  • CHO cells expressing mMTf exhibited a 3-fold increase in motility, migration, and invasion.
  • Monoclonal antibody L235 and sMTf inhibited mMTf-mediated increases in cell migration and invasion.

Conclusions:

  • mMTf functions as a cell surface receptor for plasminogen.
  • mMTf plays a key role in regulating plasminogen activation at the cell surface.
  • mMTf significantly contributes to cell migration, invasion, and motility, suggesting its involvement in cancer progression.

Related Concept Videos

Cancer Cell Migration through Invadopodia01:35

Cancer Cell Migration through Invadopodia

Invadosome is a broad category of cell surface structures with proteolytic activity that  degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However, invadopodia can...
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Activation of Integrins01:15

Activation of Integrins

Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding events provide an effective stimulus.
Metastasis02:30

Metastasis

Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
Cell Migration01:19

Cell Migration

Cell migration is a process by which the cells move from one location to another, playing an essential role in embryological development, repair and regeneration, immune response, and metastasis. Cells migrate in response to chemical or mechanical signals generated by specific organs or tissues. The overall mechanism includes three steps - polarization, protrusion, and release. Polarization involves the formation of a distinct cell front and rear, which determines the direction of movement.
Cell Migration01:09

Cell Migration

Cell migration, the process by which cells move from one location to another, is essential for the proper development and viability of organisms throughout their life. When cells are not able to migrate properly to their ordained locations, various disorders may occur. For example, disruption in cell migration causes chronic inflammatory diseases such as arthritis.