Tissue invasion and metastasis: Molecular, biological and clinical perspectives

Abstract

Cancer is a key health issue across the world, causing substantial patient morbidity and mortality. Patient prognosis is tightly linked with metastatic dissemination of the disease to distant sites, with metastatic diseases accounting for a vast percentage of cancer patient mortality. While advances in this area have been made, the process of cancer metastasis and the factors governing cancer spread and establishment at secondary locations is still poorly understood. The current article summarizes recent progress in this area of research, both in the understanding of the underlying biological processes and in the therapeutic strategies for the management of metastasis. This review lists the disruption of E-cadherin and tight junctions, key signaling pathways, including urokinase type plasminogen activator (uPA), phosphatidylinositol 3-kinase/v-akt murine thymoma viral oncogene (PI3K/AKT), focal adhesion kinase (FAK), β-catenin/zinc finger E-box binding homeobox 1 (ZEB-1) and transforming growth factor beta (TGF-β), together with inactivation of activator protein-1 (AP-1) and suppression of matrix metalloproteinase-9 (MMP-9) activity as key targets and the use of phytochemicals, or natural products, such as those from Agaricus blazei, Albatrellus confluens, Cordyceps militaris, Ganoderma lucidum, Poria cocos and Silybum marianum, together with diet derived fatty acids gamma linolenic acid (GLA) and eicosapentanoic acid (EPA) and inhibitory compounds as useful approaches to target tissue invasion and metastasis as well as other hallmark areas of cancer. Together, these strategies could represent new, inexpensive, low toxicity strategies to aid in the management of cancer metastasis as well as having holistic effects against other cancer hallmarks.

Vitronectin and dermcidin serum levels predict the metastatic progression of AJCC I–II early‐stage melanoma

“…Adhesion molecules are strong candidates to be involved in the metastatic spread of melanoma 30. PG, also known as γ‐catenin,31, 32 is a component of adherens junctions and desmosomes, and it plays an important role in Wnt/β‐catenin signaling 33, 34.…”

Small cell lung cancer: Recruitment of macrophages by circulating tumor cells

“…67 The present data indicate that CTCs in SCLC recruit macrophages through monocyte differentiation with high efficacy. 6 Comparison of the density of monocytes in control HEK293-CM treated PBMNCs with recombinant CHI3L1 exposed cells indicated that most of the monocytes differentiate to macrophages. The HEK293 cell line was selected since it expresses no significant amounts of GM-CSF and G-CSF, in good correspondence with the two CTC lines (R&D cytokine array; data not shown).…”

“…5 Thus cancers and, possibly, CTCs recruit immunosuppressive cells, particularly belonging to the myeloidmacrophage lineage, which undergo functional polarization in dependence of tumor-derived factors. 6 These "tumor-educated" macrophages promote invasion, intravasation as well as survival in the circulation and durable growth at secondary lesions. 5,7 TAMs are recruited by various cytokines and chemokines, suppress the activity of cytotoxic T-lymphocytes via programmed cell death 1 ligand 1 (PD-L1) or B7-H4 and other receptors/mediators.…”

Circulating tumor cell interactions with macrophages: implications for biology and treatment

“…Tumors and, possibly, CTCs educate macrophages to promote invasion, intravasation as well as survival in the circulation and durable growth at secondary lesions (3,29,30). The invasiveness of tumor cells was dramatically enhanced when they were cocultured with macrophages or macrophage conditioned medium (31).…”