The relationship between angiogenesis and the immune response in carcinogenesis and the progression of malignant disease

Our plain-English summary of The relationship between angiogenesis and the immune response in carcinogenesis and the progression of malignant disease, by K.J. O'Byrne, A.G. Dalgleish, M.J. Browning, et al (European Journal of Cancer, 2000).

The study

• Authors: K.J. O'Byrne, A.G. Dalgleish, M.J. Browning, W.P. Steward, A.L. Harris
• Journal: European Journal of Cancer
• Published: 2000;36(2):151-69
• Type of article: Review
• Cited by: 155 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Recent studies have demonstrated that angiogenesis and suppressed cell-mediated immunity (CMI) play a central role in the pathogenesis of malignant disease facilitating tumour growth, invasion and metastasis. In the majority of tumours, the malignant process is preceded by a pathological condition or exposure to an irritant which itself is associated with the induction of angiogenesis and/or suppressed CMI. These include: cigarette smoking, chronic bronchitis and lung cancer; chronic oesophagitis and oesophageal cancer; chronic viral infections such as human papilloma virus and ano-genital cancers, chronic hepatitis B and C and hepatocellular carcinoma, and Epstein-Barr virus (EBV) and lymphomas; chronic inflammatory conditions such as Crohn's disease and ulcerative colitis and colorectal cancer; asbestos exposure and mesothelioma and excessive sunlight exposure/sunburn and malignant melanoma. Chronic exposure to growth factors (insulin-like growth factor-I in acromegaly), mutations in tumour suppressor genes (TP53 in Li Fraumeni syndrome) and long-term exposure to immunosuppressive agents (cyclosporin A) may also give rise to similar environments and are associated with the development of a range of solid tumours. The increased blood supply would facilitate the development and proliferation of an abnormal clone or clones of cells arising as the result of: (a) an inherited genetic abnormality; and/or (b) acquired somatic mutations, the latter due to local production and/or enhanced delivery of carcinogens and mutagenic growth factors. With progressive detrimental mutations and growth-induced tumour hypoxia, the transformed cell, to a lesser or greater extent, may amplify the angiogenic process and CMI suppression, thereby facilitating further tumour growth and metastasis. There is accumulating evidence that long-term treatment with cyclo-oxygenase inhibitors (aspirin and indomethacin), cytokines such as interferon-alpha, anti-oestrogens (tamoxifen and raloxifene) and captopril significantly reduces the incidence of solid tumours such as breast and colorectal cancer. These agents are anti-angiogenic and, in the case of aspirin, indomethacin and interferon-alpha have proven immunomodulatory effects. Collectively these observations indicate that angiogenesis and suppressed CMI play a central role in the development and progression of malignant disease.

In plain English

This article was a review, not a new study, and it presented no new data. The authors drew together published laboratory, animal and human research on angiogenesis (the growth of new blood vessels) and on suppression of cell-mediated immunity, one branch of the immune system. They argued that most cancers are preceded by a condition or exposure linked to one or both processes. Their examples included cigarette smoking, chronic viral infections, sunlight, and asbestos exposure and mesothelioma. Asbestos received only brief mention, citing an earlier review. The authors wrote that angiogenesis plays a role in pleural plaque formation after asbestos exposure and has been postulated to contribute to mesothelioma. They also wrote that the immune signalling molecule IL-6 is overexpressed with asbestos exposure, and noted that the virus SV-40 had been implicated in mesothelioma. They described other researchers' reports that long-term aspirin use reduced colorectal cancer incidence by as much as 45%. The authors concluded that angiogenesis and suppressed cell-mediated immunity play a central role in the development and progression of malignant disease.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review of published literature; no original data
• Who was studied: No study population of its own; the authors reviewed published laboratory, animal and human studies
• Exposure: Many cancer-predisposing conditions and exposures, including asbestos exposure in relation to mesothelioma; no fiber type, dose or occupation is specified
• Main results:
  • Citing other work, the review stated that angiogenesis plays a role in pleural plaque formation after exposure of the mesothelium to asbestos
  • In such conditions, angiogenesis has been postulated by others to play a role in tumour development, including mesothelioma in susceptible individuals
  • The review stated that IL-6, an angiogenic cytokine, is overexpressed in conditions predisposing to cancer, including asbestos exposure
  • The review noted that the virus SV-40 had been implicated in several tumours, including mesothelioma
  • Citing other studies, the review reported that long-term aspirin use reduced colorectal cancer incidence by as much as 45%
• The authors' conclusion: The authors concluded that angiogenesis and suppressed cell-mediated immunity play a central role in the development and progression of malignant disease

Topics

Medical terms in this study, explained in our Lexicon: Angiogenesis, Carcinogenesis, Metastasis, Lung Cancer, Esophageal Cancer, Carcinoma, Colorectal Cancer, Asbestos Exposure.

Related studies

• Tumor necrosis correlates with angiogenesis and is a predictor of poor prognosis in malignant mesothelioma — J.G. Edwards, D.E. Swinson, et al. (2003)
• Beyond foreign-body-induced carcinogenesis: impact of reactive oxygen species derived from inflammatory cells in tumorigenic conversion and tumor progression — F. Okada (2007)
• VEGF and VEGF type C play an important role in angiogenesis and lymphangiogenesis in human malignant mesothelioma tumours — Y. Ohta, V. Shridhar, et al. (1999)
• Induction of angiogenesis by intraperitoneal injection of asbestos fibers — R.M. Branchaud, J.L. MacDonald, et al. (1989)
• Combination of onconase and dihydroartemisinin synergistically suppresses growth and angiogenesis of non-small-cell lung carcinoma and malignant mesothelioma — R. Shen, J. Li, et al. (2016)
• Brain-derived neurotrophic factor, a new soluble biomarker for malignant pleural mesothelioma involved in angiogenesis — P. Smeele, S.M. d'Almeida, et al. (2018)

Browse more research in European Journal of Cancer, or return to medical research.