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Tumor–Stroma Interaction and Cancer Progression

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Interaction of Immune and Cancer Cells

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Abstract

The understanding of how normal cells transform into tumor cells and progress to invasive cancer and metastases continues to evolve. The tumor mass is comprised of a heterogeneous population of cells that include recruited host immune cells, stromal cells, matrix components, and endothelial cells. This tumor microenvironment plays a fundamental role in the acquisition of hallmark traits, and has been the intense focus of current research. A key regulatory mechanism triggered by these tumor–stroma interactions includes processes that resemble epithelial–mesenchymal transition, a physiologic program that allows a polarized epithelial cell to undergo biochemical and cellular changes and adopt mesenchymal cell characteristics. These cellular adaptations facilitate enhanced migratory capacity, invasiveness, elevated resistance to apoptosis, and greatly increased production of ECM components. Indeed, it has been postulated that cancer cells undergo epithelial–mesenchymal transition to invade and metastasize.

In the following discussion, the physiology of chronic inflammation, wound healing, fibrosis, and tumor invasion will be explored. The key regulatory cytokines transforming growth factor-β and osteopontin and their roles in cancer metastasis will be highlighted.

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Abbreviations

bFGF:

Basic fibroblast growth factor

BM:

Basement membrane

BSP:

Bone sialoprotein

CSC:

Cancer stem cell

CSF-1:

Colony-stimulating factor

DMP1:

Dentin matrix protein 1

DSPP:

Dentin sialoprotein

ECM:

Extracellular matrix

EGF:

Epidermal growth factor

EMT:

Epithelial–mesenchymal transition

GAG:

Glycosaminoglycan

GMCSF:

Granulocyte–macrophage colony-stimulating factor

HCC:

Hepatocellular carcinoma

HCV:

Hepatitis C virus

Hh:

Hedgehog

HSC:

Hepatic stellate cells

IFN:

Interferon

IL:

Interleukin

LEF:

Lymphoid enhancer factor

LLC:

Large latency complex

LOX:

Lysyl oxidase

LPS:

Lipopolysaccharide

MAPK:

Mitogen-activated protein kinase

MDCK:

Madin–Derby canine kidney

MDSC:

Myeloid-derived suppressor cell

MEPE:

Matrix extracellular phoshoglycoprotein

MET:

Mesenchymal–epithelial transition

MHC:

Major histocompatibility complex

MIF:

Macrophage migration inhibitory factor

miR:

microRNA

MSC:

Mesenchymal stem cell

NK:

Natural killer

OPN:

Osteopontin

PDGF:

Platelet-derived growth factor

PMA:

Phorbol 12-myristate 13-acetate

SIBLING:

Small integrin-binding ligand N-linked glycoprotein

TAM:

Tumor-associated macrophages

TGF-β:

Transforming growth factor

TME:

Tumor microenvironment

TNF:

Tumor necrosis factor

UUO:

Unilateral ureteral obstruction

VEGF:

Vascular endothelial growth factor

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Authors and Affiliations

  1. Loyola University Medical Center, 2160 S. First Avenue, Maywood, IL, 60153, USA

    Neill Y. Li, Paul C. Kuo & Philip Y. Wai

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  1. Neill Y. Li
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  2. Paul C. Kuo
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  3. Philip Y. Wai
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Correspondence to Paul C. Kuo .

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  1. Institute of Medical Biology Polish Academy of Sciences, Lodz, Poland

    Magdalena Klink

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Li, N.Y., Kuo, P.C., Wai, P.Y. (2014). Tumor–Stroma Interaction and Cancer Progression. In: Klink, M. (eds) Interaction of Immune and Cancer Cells. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1300-4_2

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