Pathophysiology of colorectal peritoneal carcinomatosis: Role of the peritoneum

Table 1 General overview molecules/molecular pathways involved in the peritoneal metastatic cascade

Steps peritoneal metastatic cascade	Molecules/molecular pathways
Detachment from the primary tumor	Spontaneous tumor cell shedding:
	E-cadherin ↓
	N-cadherin ↑
	EMT
	PC1 and PC2 ↑
	Interstitial fluid pressure ↑
	Peroperative seeding tumor cells during surgery
Peritoneal transport	Muscinous ascites
	Actin microfilament system
	Lammelipodia, filipodia
Attachment to distant peritoneum	Transmesothelial dissemination:
	ICAM-1 ↑, PECAM-1, VCAM-1 ↑
	TNF-α, IL-1β, IL-6, IFN-γ
	β1 integrin subunit
	CD43, CD44
	Hyaluronan
	Translymphatic dissemination:
	Lymphatic stomata
	Milky spots
Invasion into the subperitoneal space	Rounding of mesothelial cells:
	HGF/SF ↑
	c-Met ↑
	Destruction of the mesothelial monolayer:
	Tumor-induced apoptosis
	Fas ligand/Fas
	Adherence to the basement membrane:
	Integrines
	Invasion of the peritoneal-blood barrier:
	MMP-1, MMP-2, MMP-7, MMP-9, MMP-13, MMP-14 ↑
	TIMP-1, TIMP-2, TIMP-3, TIMP-4
	uPA/uPAR
	plasminogen activator inhibitor -1 and -2
Proliferation and angiogenesis	Proliferation:
	EGFR, EGF, TGFα
	IGF-1, IGF-Binding Protein-3
	Angiogenesis:
	HIF-1α, HIF-1β
	VEGF/VEGFR

E-cadherin: Epithelial-cadherin; N-cadherin: Neural-cadherin; EMT: Epithelial to mesenchyme transition; PC: Polycystin; ICAM: Intercellular adhesion molecule-1; PECAM: Platelet-endothelial cell adhesion molecule-1; VCAM-1: Vascular adhesion molecule-1; TNF-α: Tumor necrosis factor-α; IL-1β: Interleukin-1β; IL-6: Interleukin-6; IFN-γ: Interferon-γ; CD43: Sialophorin; HGF: Hepatocyte growth factor; SF: Scatter factor; MMP: Matrix metalloproteinases; TIMP: Tissue inhibitor metalloproteinases; uPA: Urokinase plasminogen activator; uPAR: Urokinase plasminogen activator receptor; EGFR: Epidermal growth factor receptor; EGF: Epidermal growth factor; TGFα: Tumor growth factor α; IGF-1: Insulin like growth factor-1; HIF: Hypoxia inducible factor; VEGF: Vascular endothelial growth factor; VEGFR: Vascular endothelial growth factor receptor.