Multiple pathways of cell invasion are regulated by multiple families of serine proteases

Mario Del Rosso, Gabriella Fibbi, Marco Pucci, Silvia D'Alessio, Angela Del Rosso, Lucia Magnelli, Vincenzo Chiarugi

Research output: Contribution to journalArticle

99 Citations (Scopus)

Abstract

The complex process of tumor invasion requires the coordinated expression and activity of cell-substratum adhesive interactions and of cell-associated protease systems, which destroy the extracellular matrix (ECM), in order to enable the invading cells to simultaneously grip and destroy the anatomical barriers that control cell spreading. A number of data indicate that such a 'grip and go' process may be performed by an enlarging series of cell membrane-associated serine proteases and serine protease receptors, which provide the invasive cells with a functional unit (the protease and its receptor), able to mediate cell-substratum adhesion through specific receptor domains, to proteolytically degrade ECM and to deliver into the cell signals that up-regulate the expression either of the protease/receptor complex, or of other adhesion molecules, such as integrins. There is evidence that some proteases and protease receptor expression are under the control of tumor hypoxia, which is the result of an imbalance in oxygen supply and demand. The urokinase-type plasminogen activator (u-PA) receptor (u-PAR) is under hypoxic control and cooperates with other serine proteases of the blood coagulation pathways that may extravasate in the tumor milieu as a result of hypoxia-simulated increase of vessel permeability. Other serine proteases and their receptors cooperate with the cell-associated fibrinolytic system to promote cell invasion. Among these, tissue factor and its ligand coagulation factor VII, thrombin and its protease-activated receptors, and type II transmembrane serine proteases seem to play a crucial role. This Review takes into consideration the complex scenario of the single serine proteases and related receptors that are involved in cell invasion, as well as the protease receptor/adhesion molecule interplay which is necessary to focus the cell surface-driven proteolysis where adhesion provides a grip to the invading cell.

Original languageEnglish
Pages (from-to)193-207
Number of pages15
JournalClinical & Experimental Metastasis
Volume19
Issue number3
DOIs
Publication statusPublished - 2002

Fingerprint

Serine Proteases
Peptide Hydrolases
Hand Strength
Extracellular Matrix
Proteinase-Activated Receptors
Urokinase Plasminogen Activator Receptors
Factor VII
Thromboplastin
Blood Coagulation
Cell Adhesion
Integrins
Thrombin
Cell Communication
Adhesives
Proteolysis
Permeability
Neoplasms
Up-Regulation
Cell Membrane
Oxygen

Keywords

  • PARs
  • Serine proteases
  • Thrombin
  • Tissue factor
  • Type-II transmembrane serine proteases
  • u-PA
  • u-PAR

ASJC Scopus subject areas

  • Cancer Research

Cite this

Multiple pathways of cell invasion are regulated by multiple families of serine proteases. / Del Rosso, Mario; Fibbi, Gabriella; Pucci, Marco; D'Alessio, Silvia; Del Rosso, Angela; Magnelli, Lucia; Chiarugi, Vincenzo.

In: Clinical & Experimental Metastasis, Vol. 19, No. 3, 2002, p. 193-207.

Research output: Contribution to journalArticle

Del Rosso, Mario ; Fibbi, Gabriella ; Pucci, Marco ; D'Alessio, Silvia ; Del Rosso, Angela ; Magnelli, Lucia ; Chiarugi, Vincenzo. / Multiple pathways of cell invasion are regulated by multiple families of serine proteases. In: Clinical & Experimental Metastasis. 2002 ; Vol. 19, No. 3. pp. 193-207.
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