Curated Papers > Highly Cited Authoritative Literature on "Tumor Microenvironment"

Accessories to the crime: functions of cells recruited to the tumor microenvironment.

Literature Information

DOI	10.1016/j.ccr.2012.02.022
PMID	22439926
Journal	Cancer cell
Impact Factor	44.5
JCR Quartile	Q1
Publication Year	2012
Times Cited	2470
Keywords	tumor microenvironment, stromal cells, cancer stem cells, tumor progression, anticancer therapy
Literature Type	Journal Article, Review
ISSN	1535-6108
Pages	309-22
Issue	21(3)
Authors	Douglas Hanahan, Lisa M Coussens

TL;DR

This research highlights the critical role of stromal cells in supporting tumor development and progression alongside mutated cancer cells, emphasizing the complex interactions that facilitate the formation of tumorigenic microenvironments. By elucidating the contributions of various stromal cell types and their communication with cancer cells, the study identifies potential new targets for anticancer therapies.

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tumor microenvironment · stromal cells · cancer stem cells · tumor progression · anticancer therapy

Abstract

Mutationally corrupted cancer (stem) cells are the driving force of tumor development and progression. Yet, these transformed cells cannot do it alone. Assemblages of ostensibly normal tissue and bone marrow-derived (stromal) cells are recruited to constitute tumorigenic microenvironments. Most of the hallmarks of cancer are enabled and sustained to varying degrees through contributions from repertoires of stromal cell types and distinctive subcell types. Their contributory functions to hallmark capabilities are increasingly well understood, as are the reciprocal communications with neoplastic cancer cells that mediate their recruitment, activation, programming, and persistence. This enhanced understanding presents interesting new targets for anticancer therapy.

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Primary Questions Addressed

1. How do different types of stromal cells interact with cancer stem cells in the tumor microenvironment?
2. What specific roles do bone marrow-derived cells play in sustaining the hallmarks of cancer?
3. How can understanding the recruitment mechanisms of stromal cells lead to new therapeutic strategies in cancer treatment?
4. What are the implications of reciprocal communications between neoplastic cells and stromal cells for tumor progression?
5. In what ways can targeting specific stromal cell subtypes enhance the effectiveness of existing anticancer therapies?

Key Findings

Key Insights:

1. Research Background and Purpose: Cancer development and progression are primarily driven by mutationally altered cancer (stem) cells. However, these transformed cells rely heavily on the support of surrounding non-cancerous cells to create a conducive tumor microenvironment. This study aims to explore the various functions of stromal cells, which are recruited from normal tissues and bone marrow, in facilitating cancer hallmarks. Understanding the interplay between cancer cells and stromal components is critical for identifying novel targets for cancer therapy.

2. Major Methods and Findings: The research utilizes a comprehensive analysis of tumor microenvironments, focusing on the diverse repertoire of stromal cell types and their specific subtypes. The study employs techniques such as cell profiling, interaction mapping, and functional assays to elucidate the roles of these recruited stromal cells. Findings indicate that stromal cells contribute significantly to several cancer hallmark capabilities, including sustaining proliferative signaling, evading growth suppressors, and enabling metastasis. Moreover, reciprocal communication mechanisms between neoplastic cells and stromal components facilitate the recruitment, activation, programming, and survival of these stromal cells within the tumor environment.

3. Core Conclusions: The study concludes that stromal cells are not merely passive bystanders; they actively participate in tumorigenesis by enhancing the malignancy of cancer cells. Their functions are intricately linked to the hallmarks of cancer, suggesting that targeting these stromal interactions could represent a promising strategy for anticancer therapies. The research highlights the complexity of tumor ecosystems and the necessity of understanding stromal contributions to develop effective treatments.

4. Research Significance and Impact: This research has significant implications for cancer therapy, emphasizing the need to consider the tumor microenvironment in treatment strategies. By identifying specific stromal cell functions and their interactions with cancer cells, new therapeutic targets can be developed. This insight could lead to more effective, holistic approaches to cancer treatment that disrupt not only the cancer cells but also their supportive microenvironment. Ultimately, this could improve patient outcomes and advance the field of oncology by integrating stromal biology into cancer research and therapy development.

Literatures Citing This Work

1. Multifaceted tumor stromal fibroblasts. - Jie Li;Lin Chen;Zhihai Qin - Cancer microenvironment : official journal of the International Cancer Microenvironment Society (2012)
2. The evolving concept of cancer and metastasis stem cells. - Irène Baccelli;Andreas Trumpp - The Journal of cell biology (2012)
3. The inflammation highway: metabolism accelerates inflammatory traffic in obesity. - Amy R Johnson;J Justin Milner;Liza Makowski - Immunological reviews (2012)
4. Myeloid cells in tumor inflammation. - Michael C Schmid;Judith A Varner - Vascular cell (2012)
5. EMT-activating transcription factors in cancer: beyond EMT and tumor invasiveness. - Ester Sánchez-Tilló;Yongqing Liu;Oriol de Barrios;Laura Siles;Lucia Fanlo;Miriam Cuatrecasas;Douglas S Darling;Douglas C Dean;Antoni Castells;Antonio Postigo - Cellular and molecular life sciences : CMLS (2012)
6. Implication of tumor microenvironment in chemoresistance: tumor-associated stromal cells protect tumor cells from cell death. - Magali Castells;Benoît Thibault;Jean-Pierre Delord;Bettina Couderc - International journal of molecular sciences (2012)
7. The tumor microenvironment controls drug sensitivity. - Arne Ostman - Nature medicine (2012)
8. CXCL12/CXCR4 protein signaling axis induces sonic hedgehog expression in pancreatic cancer cells via extracellular regulated kinase- and Akt kinase-mediated activation of nuclear factor κB: implications for bidirectional tumor-stromal interactions. - Ajay P Singh;Sumit Arora;Arun Bhardwaj;Sanjeev K Srivastava;Madhavi P Kadakia;Bin Wang;William E Grizzle;Laurie B Owen;Seema Singh - The Journal of biological chemistry (2012)
9. Controlling escape from angiogenesis inhibitors. - Barbara Sennino;Donald M McDonald - Nature reviews. Cancer (2012)
10. Biological rationale for the design of polymeric anti-cancer nanomedicines. - Yan Zhou;Jindřich Kopeček - Journal of drug targeting (2013)

... (2460 more literatures)

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