Lipoprotein[a] and cancer: anti-neoplastic effect besides its cardiovascular potency.
While the death rate from cancer has substantially decreased over the past decade, the search for effective and tolerable therapies is a great challenge as yet. The evidence that malignant cells cannot grow to a clinically detectable tumor mass and spread in the absence of an adequate vascular support, has opened a new area of research towards the selective inhibition or even destruction of tumor vessels. Angiostatin and angiostatin-related proteins are a family of specific angiogenesis inhibitors produced by tumors from a family of naturally occurring proteins, which also includes plasminogen and lipoprotein[a]. The anti-angiogenic activity of these proteins resides in cryptic and highly-repetitive molecular domains hidden within the protein moiety, called kringles. Lipoprotein[a] is an intriguing molecule consisting of a low-density lipoprotein core in addition to the covalently bound apolipoprotein[a]. Apolipoprotein[a] is characterized by an inactive protease domain, a single copy of the plasminogen kringle V and multiple repeats of domains homologous to the plasminogen kringle IV. Reliable studies on animal models indicate that the proteolytic break-down products of apolipoprotein[a] would posses anti-angiogenic and anti-tumoral properties both in vitro and in vivo, a premise to develop novel therapeutic modalities which may efficiently suppress tumor growth and metastasis. This review is focused on the biochemical structure, metabolism and the anti-angiogenic activity of this unique and elusive kringle-containing lipoprotein.
Lippi
Giuseppe
G
Sezione di Chimica e Microscopia Clinica, Dipartimento di Scienze Morfologico-Biomediche, Università degli Studi di Verona, Ospedale Policlinico G.B. Rossi, Piazzale Scuro 10, 37134 Verona, Italy. giuseppe.lippi@univr.it
Franchini
Massimo
M
Salvagno
Gian Luca
GL
Guidi
Gian Cesare
GC
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D043168:Angiostatins / Q000494:pharmacology; D000818:Animals; D001157:Arterial Occlusive Diseases / Q000209:etiology; D006801:Humans; D017270:Lipoprotein(a) / Q000097:blood / Q000235:genetics / Q000502:physiology / Q000627:therapeutic use*; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy*
D020533:Angiogenesis Inhibitors; D017270:Lipoprotein(a); D043168:Angiostatins