Stromal cell

Stromal cells are connective tissue cells of any organ, for example in the uterine mucosa (endometrium), prostate, bone marrow, lymph node and the ovary. They are cells that support the function of the parenchymal cells of that organ. The most common stromal cells include fibroblasts and pericytes. The term stromal comes from Latin stromat-, “bed covering”, and Ancient Greek στρῶμα, strôma, “bed”.

The interaction between stromal cells and tumor cells is known to play a major role in cancer growth and progression.[1] In addition, by regulating local cytokine networks (e.g. M-CSF,[2] LIF[3]), bone marrow stromal cells have been described to be involved in human haematopoiesis and inflammatory processes.

Stromal cells (in the dermis layer) adjacent to the epidermis (the top layer of the skin) release growth factors that promote cell division. This keeps the epidermis regenerating from the bottom while the top layer of cells on the epidermis are constantly being "sloughed" off the body. Additionally, stromal cells play a role in inflammation responses, and controlling the amount of cells accumulating at an inflamed region of tissue.[4]

In Cancer

During normal wound healing processes, the local stromal cells change into reactive stroma after altering their phenotype. However, under certain conditions, tumor cells can convert these reactive stromal cells further and transition them into tumor-associated stromal cells (TASCs) [5]. In comparison to non-reactive stromal cells, TACs secrete increased levels of proteins and matrix metalloproteinases (MMPs). These proteins include fibroblast activating protein and alpha-smooth muscle actin. Furthermore, TACs secrete many pro-tumorigenic factors such as vascular endothelial growth factor (VEGF), stromal-derived factor-1 alpha, IL-6, IL-8, tenascin-C, and others. These factors are known to recruit additional tumor and pro-tumorigenic cells.

The cross-talk between the host stroma and tumor cells is essential for tumor growth and progression. Tumor stromal production exhibits similar qualities as normal wound repair such as new blood vessel formation, immune cell and fibroblast infiltration, and considerable remodeling of the extracellular matrix. Additionally, the recruitment of local normal host stromal cells, such as bone marrow mesenchymal stromal cells, endothelial cells, and adipocytes, help create a conspicuously heterogeneous composition. Furthermore, these cells secrete an abundance of factors that help regulate tumor development. Potential targets for tumor-associated stromal cell recruitment have been identified in the following host tissue: bone marrow, connective tissue, adipose tissue, and blood vessels. Moreover, evidence suggests that tumor-associated stroma are a prerequisite for metastasis and tumor cell invasion. These are known to arise from at least six different origins: immune cells, macrophages, adipocytes, fibroblasts, pericytes, and bone marrow mesenchymal stromal cells [6].

Furthermore, the tumor stroma is primarily composed of the basement membrane, fibroblasts, extracellular matrix, immune cells, and blood vessels. Typically, most host cells in the stroma are characterized by tumor-suppressive abilities. However, during malignancy, the stroma will undergo alterations to consequently incite growth, invasion, and metastasis. These changes include the formation of carcinoma-associated fibroblasts (CAFs) which comprises a major portion of the reactive tissue stroma and plays a critical role in regulating tumor progression [7].

Certain types of skin cancers (basal cell carcinomas) cannot spread throughout the body because the cancer cells require nearby stromal cells to continue their division. The loss of these stromal growth factors when the cancer moves throughout the body prevents the cancer from invading other organs.

Stroma is made up of the non-malignant cells, but can provide an extracellular matrix on which tumor cells can grow. Stromal cells may also limit T-cell proliferation via nitric oxide production, hindering immune capability.[8]

See also

References
  1. Wiseman BS, Werb Z (May 2002). "Stromal effects on mammary gland development and breast cancer" (PDF). Science. 296 (5570): 1046–9. doi:10.1126/science.1067431. PMC 2788989. PMID 12004111. Archived from the original (PDF) on 2010-06-28.
  2. Fixe, Philippe (1997). "Spontaneous and inducible production of macrophage colony-stimulating factor by human bone marrow stromal cells". European Cytokine Network. 8 (1): 91–5. PMID 9110154.
  3. LORGEOT, Valérie (28 February 1997). "Spontaneous and Inducible Production of Leukaemia Inhibitory Factor by Human Bone Marrow Stromal Cells". Cytokine. 9 (10): 754–758. doi:10.1006/cyto.1997.0225. PMID 9344507.
  4. Buckley, C. D.; Barone, F.; Nayar, S.; Bénézech, C.; Caamaño, J. (2015). "Stromal cells in chronic inflammation and tertiary lymphoid organ formation". Annual Review of Immunology. 33: 715–45. doi:10.1146/annurev-immunol-032713-120252. PMID 25861980.
  5. Bussard, Karen; Mutkus, Lysette; Stumpf, Kristina. "Tumor-associated stromal cells as key contributors to the tumor microenvironment". Breast Cancer Research. 18 (84). doi:10.1186/s13058-016-0740-2.
  6. Bussard, Karen; Mutkus, Lysette; Stumpf, Kristina. "Tumor-associated stromal cells as key contributors to the tumor microenvironment". Breast Cancer Research. 18 (84). doi:10.1186/s13058-016-0740-2.
  7. Bremnes, Roy; Dønnem, Tom; Al-Saad, Samer; Al-Shibli, Khalid. "The Role of Tumor Stroma in Cancer Progression and Prognosis: Emphasis on Carcinoma-Associated Fibroblasts and Non-small Cell Lung Cancer". Journal of Thoracic Oncology. 6 (1): 209–217.
  8. "Stromal cells put the brakes on T-cell responses". Retrieved 5 July 2018.
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