Tumor microenvironment complexity and therapeutic implications at a glance

Abstract

The dynamic interactions of cancer cells with their microenvironment consisting of stromal cells (cellular part) and extracellular matrix (ECM) components (non-cellular) is essential to stimulate the heterogeneity of cancer cell, clonal evolution and to increase the multidrug resistance ending in cancer cell progression and metastasis. The reciprocal cell-cell/ECM interaction and tumor cell hijacking of non-malignant cells force stromal cells to lose their function and acquire new phenotypes that promote development and invasion of tumor cells. Understanding the underlying cellular and molecular mechanisms governing these interactions can be used as a novel strategy to indirectly disrupt cancer cell interplay and contribute to the development of efficient and safe therapeutic strategies to fight cancer. Furthermore, the tumor-derived circulating materials can also be used as cancer diagnostic tools to precisely predict and monitor the outcome of therapy. This review evaluates such potentials in various advanced cancer models, with a focus on 3D systems as well as lab-on-chip devices.

Heparan Sulfate Proteoglycan Signaling in Tumor Microenvironment

“…Specific domains of proteoglycan core and/or HS chains as well as HSPG synthetizing and remodeling enzymes represent potential therapeutic targets [205]. Among the explored approaches, there is the use of high-affinity antibodies recognizing functional epitopes of HSPGs, HS mimetic compounds, cationic proteins which interact with the highly anionic sulfate and carboxylate moieties of HS chains, natural and synthetic peptides, small organic molecules that may affect either HSPG-protein interactions and subsequent signaling or the HSPG biosynthetic machinery [4][5][6]29,32,37,155,156,165,[239][240][241][242][243]. Some examples of HSPG targeting-based therapeutics for cancer treatment are reported in Table 4.…”

“…Complex and dynamic interactions between tumor cells and their microenvironment, involving cell-cell and cell-ECM contacts and the activity of soluble factors that enable these contacts, are essential to promote tumor growth, invasion, and metastasis [1][2][3]. Hence, due to the compelling role of tumor microenvironment in carcinogenesis, therapeutic strategies targeting tumor microenvironment components that interfere with the complex crosstalk between tumor cells, host cells, and their surrounding ECM are being explored [4][5][6].…”

Development of an Engineered Peptide Antagonist against Periostin to Overcome Doxorubicin Resistance in Breast Cancer

“…BCA cells, approximately 1x10 5 cells, were plated on top of coverslips in 24-well plates and cultured for 24 h. After that, media was removed and cells were washed with PBS, xed with 4% paraformaldehyde, washed again and blocked with 5% FBS. The primary antibody used was mouse antihuman integrin aVβ5 monoclonal antibody (MAB2019Z, Sigma-Aldrich, Merck KGaA, Darmstadt, Germany), at a concentration of 15 mg/ml and incubated with the cells at 37 o C for 4 h. After that, cells were washed with PBS and incubated with Cy™3 A niPure F(ab') 2 Thermo Fisher Scienti c). Continuously, 10 10 plaque forming units (pfu) of bacteriophage were poured into the wells and incubated at room temperature for 1 h. Unbound phages were then washed off and bound phages were collected.…”

Bone Microenvironment and Osteosarcoma Metastasis

“…The bone microenvironment is also a fertile soil and a complex biological system that facilitates the metastasis of many cancers including osteosarcoma (OS) [ 8 , 9 ]. In recent years, to understand the progress of OS, a number of studies have focused on the relationship between OS and the bone microenvironment, for example, MSCs, which are one of the most important members in the bone microenvironment [ 10 ].…”