The Multifaceted Role of Plasminogen in Cancer

Abstract

Fibrinolytic factors like plasminogen, tissue-type plasminogen activator (tPA), and urokinase plasminogen activator (uPA) dissolve clots. Though mere extracellular-matrix-degrading enzymes, fibrinolytic factors interfere with many processes during primary cancer growth and metastasis. Their many receptors give them access to cellular functions that tumor cells have widely exploited to promote tumor cell survival, growth, and metastatic abilities. They give cancer cells tools to ensure their own survival by interfering with the signaling pathways involved in senescence, anoikis, and autophagy. They can also directly promote primary tumor growth and metastasis, and endow tumor cells with mechanisms to evade myelosuppression, thus acquiring drug resistance. In this review, recent studies on the role fibrinolytic factors play in metastasis and controlling cell-death-associated processes are presented, along with studies that describe how cancer cells have exploited plasminogen receptors to escape myelosuppression.

Anti‐Chi3L1 antibody suppresses lung tumor growth and metastasis through inhibition of M2 polarization

“…Congenital plasminogen deficiency is a rare genetic disorder caused by an alteration in the PLG gene. Plasminogen activation plays an important role in the invasion and metastasis of lung, breast and brain cancer [ 41 , 44 , 45 ]. To determine the physical relationship between Chi3L1 and PLG, immunoprecipitation was performed using the anti‐Myc antibody.…”

Complement C4-A and Plasminogen as Potential Biomarkers for Prediction of Papillary Thyroid Carcinoma

“…PLG, a 92-94-kilodalton protein produced in the liver and circulated in the blood, is known to be involved in the degradation of extracellular matrix, cell migration, angiogenesis, oncogenesis, and metastasis (20,21). The PLG is associated autophagy of cancer (22). Fang et al demonstrated that Plasminogen kringle 5 suppressed the growth gastric cancer by inhibiting angiogenesis and apoptosis (23).…”

Notch Signaling in Breast Tumor Microenvironment as Mediator of Drug Resistance

“…ECM remodeling is influenced by proteinases, MMPs and PA–plasmin systems [ 100 , 101 ]. Plasmin, either directly or indirectly through MMPs, degrades components of the ECM, thus contributing to cancer cell invasion and metastases [ 102 ]. It is reported that MMPs are secreted and activated primarily by tumor cells but also by cellular components of the TME [ 103 ].…”