Impact of proteolytic enzymes in colorectal cancer development and progression

Table 1 Categories and main properties of proteolytic enzymes

Property	Cysteine proteases	Serine proteases	Aspartic proteases	Metallo proteases
Active site	Cysteine	Serine	Aspartic acid	Zinc
Optimum pH	7-9	3-7	2-4	5-9
Location	Lysosomes	Intra-extracellular	Lysosomes	Intra-extracellular
Examples	Cathepsins	Elastase	Pepsinogen I-II	Collagenase
	B, L, C, H	Trypsin	Cathepsins D, E	Stromelysin
		PA: uPA, tPA	Gelatinase	Matrilysin
Inhibitors	Cystatin	Antitrypsin	Unknown	TIMP
		Antithrombin III
		PAI

PA: Plasminogen activators; uPA: Uroinase-type plasminogen activator; tPA: Tissue-type plasminogen activator; PAI: Plasminogen activator inhibitor; TIMP: Tissue inhibitor of metalloproteinases.

Table 2 General roles of proteolytic enzymes in cancers

Degradation or disruption of basement membrane and extracellular matrix

Produce components which allow the in situ cancer cells to disseminate to distant organ

Formation of a complex microenvironment that promotes malignant transformation

Activation of growth factors, adhesion molecules

Suppression of tumor cell apoptosis

Destruction of chemokine gradients

Modulation of antitumor immune reactions

Dual and complex role in angiogenesis

Table 3 Clinical significance of proteolytic enzymes in colorectal cancer

Role in colorectal tumor biology, in the process of tumor invasion and metastasis

Role in malignant transformation of colorectal precancerous conditions and lesions

Potential diagnostic tool

New and independent prognostic factors

Potential tumor marker impact for early diagnosis

Potential target molecules for therapeutic agents