Cancer: a mirrored room between tumor bulk and tumor microenvironment

Abstract

It has been well documented that the tumor microenvironment (TME) plays a key role in the promotion of drug resistance, the support of tumor progression, invasiveness, metastasis, and even the maintenance of a cancer stem-like phenotype. Here, we reviewed TME formation presenting it as a reflection of a tumor’s own organization during the different stages of tumor development. Interestingly, functionally different groups of stromal cells seem to have specific spatial distributions within the TME that change as the tumor evolves into advanced stage progression which correlates with the fact that cancer stem-like cells (CSCs) are located in the edges of solid tumor masses in advanced tumors.We also focus on the continuos feedback that is established between a tumor and its surroundings. The “talk” between tumor mass cells and TME stromal cells, marks the evolution of both interlocuting cell types. For instance, the metabolic and functional transformations that stromal cells undergo due to tumor corrupting activity.Moreover, the molecular basis of metastatic spread is also approached, making special emphasis on the site-specific pre-metastatic niche formation as another reflection of the primary tumor molecular signature.Finally, several therapeutic approaches targeting primary TME and pre-metastatic niche are suggested. For instance, a systematic analysis of the TME just adjacent to the tumor mass to establish the proportion of myofibroblasts-like cancer-associated fibroblasts (CAFs) which may in turn correspond to stemness and metastases-promotion. Or the implementation of “re-education” therapies consisting of switching tumor-supportive stromal cells into tumor-suppressive ones. In summary, to improve our clinical management of cancer, it is crucial to understand and learn how to manage the close interaction between TME and metastasis.

Roles of the CXCL8-CXCR1/2 Axis in the Tumor Microenvironment and Immunotherapy

“…The tumor microenvironment (TME) has a close relationship with carcinogenesis but also provides fertile ground for tumor progression and metastasis [ 1 , 2 ]. However, our knowledge of cellular composition, organization, spatial distribution, interaction, and communication is limited concerning the TME.…”

The Molecular Basis and Therapeutic Aspects of Cisplatin Resistance in Oral Squamous Cell Carcinoma

“…The tumor microenvironment consists of the tumor cells themselves, multiple stromal cells and extracellular matrix, and is usually characterized by hypoxia, and immunosuppression (80)(81)(82). The interactions of various cells and cytokines form a complex network of mechanisms (83), and recent studies have revealed that TME is responsible for the induction of multidrug resistance in OSCC (Figure 3).…”

The Heterogeneity of the Tumor Microenvironment as Essential Determinant of Development, Progression and Therapy Response of Pancreatic Cancer

“…Thus, intratumor heterogeneity can occur and manifest on multiple levels based on the expansion of tumor cell clones with different genetic (driver as well as passenger mutations) and epigenetic alterations (hypermethylated DNA regions, histone modifications) as well as divergent differentiation stages (CSC versus non-CSC stage). These alterations in turn essentially contribute to different metabolic requirements (dependence on glucose, lactate or glutamine) as well as phenotypic diversity within the tumor mass resulting in e.g., proliferating versus resting, sessile versus motile/invasive or therapy responsive or resistant tumor cell clones [ 35 , 36 ]. Important to note, expansion and evolution of certain tumor cell clones are highly dependent on the adjacent stroma which co-evolves with the different tumor cell clones during pancreatic tumorigenesis, applying to the primary as well as to the secondary context [ 37 , 38 ].…”