ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2019
Chemotherapy-generated cell debris stimulates colon carcinoma tumor growth via osteopontin.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 43 citations in OpenAlex.
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- Immune cell changes following chemotherapy in advanced pancreatic cancer with variations based on gender.Scientific reports · 2025Article
- Cancer-associated macrophage-like cells as a prognostic biomarker in solid tumors.The journal of liquid biopsy · 2024Review
- Enhancing cancer immunotherapy via inhibition of soluble epoxide hydrolase.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Dual‑directional effect of vinorelbine combined with cisplatin or fluorouracil on tumor growth and metastasis in metronomic chemotherapy in breast cancer.International journal of oncology · 2024Article
- Role of osteopontin in cancer development and treatment.Heliyon · 2023Review
- Cell death, therapeutics, and the immune response in cancer.Trends in cancer · 2023Review
- Targeting Angiogenesis via Resolution of Inflammation.Cold Spring Harbor perspectives in medicine · 2023Review
- Synergistic Antitumor Potency of a Self-Assembling Cyclodextrin Nanoplex for the Co-Delivery of 5-Fluorouracil and Interleukin-2 in the Treatment of Colorectal Cancer.Pharmaceutics · 2023Article
- COVID-19 and cancer: start the resolution!Cancer metastasis reviews · 2022Review
- Recent Advancements in Hyperthermia-Driven Controlled Drug Delivery from Nanotherapeutics.Recent advances in drug delivery and formulation · 2022Article
- Eicosanoid regulation of debris-stimulated metastasis.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Microenvironment-triggered multimodal precision diagnostics.Nature materials · 2021Article
- Debris-stimulated tumor growth: a Pandora's box?Cancer metastasis reviews · 2021Review
- Regulation of intercellular biomolecule transfer-driven tumor angiogenesis and responses to anticancer therapies.The Journal of clinical investigation · 2021Article
- Reprograming of Tumor-Associated Macrophages in Breast Tumor-Bearing Mice under Chemotherapy by Targeting Heme Oxygenase-1.Antioxidants (Basel, Switzerland) · 2021Article
- Epigenetic Mechanisms beyond Tumour-Stroma Crosstalk.Cancers · 2021Review
- Carcinogenesis: Failure of resolution of inflammation?Pharmacology & therapeutics · 2021Review
- Breast cancer cell debris diminishes therapeutic efficacy through heme oxygenase-1-mediated inactivation of M1-like tumor-associated macrophages.Neoplasia (New York, N.Y.) · 2020Article
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Colon cancer recurrence after therapy, such as 5-fluorouracil (5-FU), remains a challenge in the clinical setting. Chemotherapy reduces tumor burden by inducing cell death; however, the resulting dead tumor cells, or debris, may paradoxically stimulate angiogenesis, inflammation, and tumor growth. Here, we demonstrate that 5-FU-generated colon carcinoma debris stimulates the growth of a subthreshold inoculum of living tumor cells in subcutaneous and orthotopic models. Debris triggered the release of osteopontin (OPN) by tumor cells and host macrophages. Both coinjection of debris and systemic treatment with 5-FU increased plasma OPN levels in tumor-bearing mice. RNA expression levels of secreted phosphoprotein 1, the gene that encodes OPN, correlate with poor prognosis in patients with colorectal cancer and are elevated in chemotherapy-treated patients who experience tumor recurrence vs. no recurrence. Pharmacologic and genetic ablation of OPN inhibited debris-stimulated tumor growth. Systemic treatment with a combination of a neutralizing OPN antibody and 5-FU dramatically inhibited tumor growth. These results demonstrate a novel mechanism of tumor progression mediated by OPN released in response to chemotherapy-generated tumor cell debris. Neutralization of debris-stimulated OPN represents a potential therapeutic strategy to overcome the inherent limitation of cytotoxic therapies as a result of the generation of cell debris.-Chang, J., Bhasin, S. S., Bielenberg, D. R., Sukhatme, V. P., Bhasin, M., Huang, S., Kieran, M. W., Panigrahy, D. Chemotherapy-generated cell debris stimulates colon carcinoma tumor growth via osteopontin.
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