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Cancer microenvironment and genomics: evolution in process

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Abstract

Cancer heterogeneity is a result of genetic mutations within the cancer cells. Their proliferation is not only driven by autocrine functions but also under the influence of cancer microenvironment, which consists of normal stromal cells such as infiltrating immune cells, cancer-associated fibroblasts, endothelial cells, pericytes, vascular and lymphatic channels. The relationship between cancer cells and cancer microenvironment is a critical one and we are just on the verge to understand it on a molecular level. Cancer microenvironment may serve as a selective force to modulate cancer cells to allow them to evolve into more aggressive clones with ability to invade the lymphatic or vascular channels to spread to regional lymph nodes and distant sites. It is important to understand these steps of cancer evolution within the cancer microenvironment towards invasion so that therapeutic strategies can be developed to control or stop these processes.

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Abbreviations

MBM:

Brain metastasis

ANGPTL4:

Angiopoietin-like 4

CysC:

Cystatin C

CLDN1:

Claudin-1

DTCs:

Disseminated tumor cells

ECM:

Extracellular matrix

MM:

Malignant melanoma

bHLH:

Helix-loop-helix

CPI:

Checkpoint inhibitors

IO:

Immunoncology

TAMPP:

T-cell activation marker proficiency panel

ROI:

Regions of interest

CNN:

Convolutional neural networks

BC:

Breast cancer

AA:

African American

EA:

White or European American

TNBC:

Triple-negative BC

ICSBCS:

International Center for the Study of Breast Cancer Subtypes

TST:

Trans-Atlantic Slave Trade

DARC/ACKR1 :

Duffy Antigen Receptor for Chemokines/Atypical Chemokine Receptor 1 gene

IMC:

Imaging mass cytometry

RNA-Seq:

RNA sequencing

GTEx:

Genotype-Tissue Expression database

Treehouse CARE:

Treehouse Comparative Analysis of RNA Expression

CRISPR/Cas9:

Clustered Regularly-Interspaced Short Palindromic Repeats

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Acknowledgements

Isaac P. Witz, Orit Sagi-Assif and Sivan Izraely thank their colleagues Shlomit Ben-Menachem and Tsipi Meshel, and the Laboratory of Tumor Microenvironment & Metastasis Research for their valuable help and support.

Funding

The research conducted by the authors is supported by the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (Needham, MA, USA).

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Authors and Affiliations

  1. California Pacific Medical Center and Research Institute, San Francisco, USA

    Stanley P. Leong

  2. The Shmunis School of Biomedicine and Cancer Research, School of Molecular Cell Biology & Biotechnology, George S. Wise Faculty of Life Science, Tel Aviv University, Tel Aviv, Israel

    Isaac P. Witz, Orit Sagi-Assif & Sivan Izraely

  3. European Center for Angioscience, Medizinische Fakultät Mannheim der Universität Heidelberg, Heidelberg, Germany

    Jonathan Sleeman

  4. Providence Portland Medical Center, Portland, USA

    Brian Piening, Bernard A. Fox & Carlo B. Bifulco

  5. Department of Surgery, Weill Cornell Medical College, New York City, NY, USA

    Rachel Martini, Lisa Newman & Melissa Davis

  6. Department of Genetics, University of Georgia, Athens, GA, USA

    Rachel Martini

  7. Department of Molecular, Cell and Developmental Biology, University of California Santa Cruz and UC Santa Cruz Genomics Institute, Santa Cruz, USA

    Lauren M. Sanders & Olena M. Vaske

  8. UC Santa Cruz Genomics Institute and Howard Hughes Medical Institute, University of California Santa Cruz, Santa Cruz, USA

    David Haussler

  9. Department of Surgery, Neurosurgery and Pediatrics, University of Arizona College of Medicine-Tucson, Tucson, AZ, USA

    Marlys Witte

Authors
  1. Stanley P. Leong
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  2. Isaac P. Witz
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  3. Orit Sagi-Assif
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  4. Sivan Izraely
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  5. Jonathan Sleeman
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  7. Bernard A. Fox
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  9. Rachel Martini
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  10. Lisa Newman
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  11. Melissa Davis
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  12. Lauren M. Sanders
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  14. Olena M. Vaske
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  15. Marlys Witte
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Contributions

Equal contribution regarding data/information collection, analysis and writing among the listed authors.

Corresponding authors

Correspondence to Melissa Davis or David Haussler.

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The authors declare that they have no conflict of interest.

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Not applicable for this review article.

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Presented at the 8th International Cancer Metastasis Congress in San Francisco, CA, USA from October 25–27, 2019 (http://www.cancermetastasis.org). To be published in an upcoming Special Issue of Clinical and Experimental Metastasis: Novel Frontiers in Cancer Metastasis.

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Leong, S.P., Witz, I.P., Sagi-Assif, O. et al. Cancer microenvironment and genomics: evolution in process. Clin Exp Metastasis 39, 85–99 (2022). https://doi.org/10.1007/s10585-021-10097-9

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  • DOI: https://doi.org/10.1007/s10585-021-10097-9

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