Solid tumour and leukemic cells expressing
chemokine receptors, metastasize to
chemokine-secreting organs.
Chemokines indirectly affect tumour development by attracting immunocompetent cells with pro- or anti-tumoral activities. Various membrane-associated and soluble
proteases selectively cleave specific
chemokines. Precursor plasma
chemokines (CXCL7, CCL14) need to be proteolytically processed to obtain receptor affinity. Angiogenic
CXC chemokines (CXCL1, CXCL8) have increased CXCR1/CXCR2 affinity after limited NH2-terminal processing, whereas truncated angiostatic
chemokines (CXCL10) show lower CXCR3 affinity without loss of angiostatic potential. NH2-terminally cleaved
monocyte chemotactic proteins (CCL2, CCL7, CCL8) have impaired capacity to attract tumour-associated macrophages and function as receptor antagonists for intact
CC chemokines. Migration of Th1/CCR5+ and Th2/CCR4+ effector lymphocytes toward CCR5 (CCL5, CCL3L1) and CCR4 (CCL22)
ligands is affected by cleavage. Although proteolytical processing of
chemokines is well studied in vitro, the direct or indirect effects on tumour invasion and
metastasis are only poorly evaluated.