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Updated: Jun 18, 2026
A Novel Stromal Fibroblast-Modulated 3D Tumor Spheroid Model for Studying Tumor-Stroma Interaction and Drug Discovery
Published on: February 28, 2020
Involvement of stromal p53 in tumor-stroma interactions
Jair Bar1, Neta Moskovits, Moshe Oren
1Division of Medical Oncology, The Ottawa Hospital Cancer Center, General Campus, Ottawa, Ontario, K1H 8L6 Canada. bar.jair@gmail.com
Abstract:
p53 is a major tumor-suppressor gene, inactivated by mutations in about half of all human cancer cases, and probably incapacitated by other means in most other cases. Most research regarding the role of p53 in cancer has focused on its ability to elicit apoptosis or growth arrest of cells that are prone to become malignant owing to DNA damage or oncogene activation, i.e. cell-autonomous activities of p53. However, p53 activation within a cell can also exert a variety of effects upon neighboring cells, through secreted factors and paracrine and endocrine mechanisms. Of note, p53 within cancer stromal cells can inhibit tumor growth and malignant progression. Cancer cells that evolve under this inhibitory influence acquire mechanisms to silence stromal p53, either by direct inhibition of p53 within stromal cells, or through pressure for selection of stromal cells with compromised p53 function. Hence, activation of stromal p53 by chemotherapy or radiotherapy might be part of the mechanisms by which these treatments cause cancer regression. However, in certain circumstances, activation of stromal p53 by cytotoxic anti-cancer agents might actually promote treatment resistance, probably through stromal p53-mediated growth arrest of the cancer cells or through protection of the tumor vasculature. Better understanding of the underlying molecular mechanisms is thus required. Hopefully, this will allow their manipulation towards better inhibition of cancer initiation, progression and metastasis.
Insights
The tumor suppressor p53 (also known as TP53) influences cancer not only within cells but also in neighboring stromal cells. Stromal p53 can inhibit tumor growth, but cancer cells may evolve to silence it, impacting treatment effectiveness.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- The tumor suppressor gene p53 is frequently inactivated in human cancers.
- Research has primarily focused on p53's cell-autonomous roles in apoptosis and growth arrest.
- Emerging evidence highlights p53's non-cell-autonomous functions in regulating the tumor microenvironment.
Purpose of the Study:
- To explore the non-cell-autonomous functions of p53 in cancer.
- To investigate how p53 in stromal cells impacts tumor growth and progression.
- To understand the mechanisms by which cancer cells interact with and potentially overcome stromal p53 activity.
Main Methods:
- Review of existing literature on p53 signaling in cancer and its microenvironment.
- Analysis of studies investigating paracrine and endocrine effects of p53.
- Examination of mechanisms of stromal p53 inactivation by cancer cells.
Main Results:
- p53 within cancer-associated stromal cells can suppress tumor growth and malignant progression.
- Cancer cells develop strategies to silence stromal p53, including direct inhibition or selection of compromised stromal cells.
- Activation of stromal p53 by therapies like chemotherapy or radiotherapy may contribute to tumor regression.
- Conversely, activated stromal p53 can sometimes promote treatment resistance by inhibiting cancer cell growth or protecting tumor vasculature.
Conclusions:
- p53 plays a critical dual role in cancer, acting both within cancer cells and in the surrounding stroma.
- Understanding stromal p53 mechanisms is crucial for developing novel cancer therapies.
- Targeting stromal p53 interactions could offer new avenues for inhibiting cancer initiation, progression, and metastasis.
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