Lewis lung carcinoma

From Wikipedia, the free encyclopedia
Jump to navigation Jump to search

Lewis lung carcinoma is a tumor that spontaneously developed as an epidermoid carcinoma in the lung of a C57BL mouse. It was discovered in 1951 by Dr. Margaret Lewis of the Wistar Institute and became one of the first transplantable tumors.[1]



According to a 2015 review article, Lewis lung carcinoma is the only reproducible syngeneic lung cancer model, meaning that it is the only reproducible lung cancer model that utilizes a transplant that is immunologically compatible. Syngeneic models have proven to be useful in predicting clinical benefit of therapy in preclinical experiments. However, there has been criticism directed towards syngeneic model usage when attempting to translate therapies from another species to humans. For example, cancer therapies that exhibited promising results in mouse models can and have failed in clinical trials due to physiological differences in the activity of the targeted gene product. The activity of the mouse product did not translate to the activity of the human counterpart. tumor originated spontaneously as a carcinoma of the lung of a C57BL mouse.[2]


Lewis lung carcinoma can also be utilized as an orthotopic model.[2] Orthotopic models focus upon correctly modeling the tumor microenvironment by injecting or implanting tumors into the corresponding organ that they originated from (i.e. implanting a Lewis lung carcinoma into the lung of another C57BL mouse). Because of this fidelity to mimicking the tumor microenvironment, orthotopic models are considered to be more physiologically relevant in representing human tumorigenesis. However, the creation of such models is a typically more involved and technically challenging process. They also require more complex imaging modalities for data collection.[3]


Generally, Lewis lung carcinoma is highly metastatic in immunocompetent mice.[4] If subcutaneously injected into mice, it is known to avidly metastasize to the lung. In fact, a 1996 study found that the carcinoma predominantly metastasized into the lungs after tail vein injections.[5] Lewis lung carcinoma has the appearance of a semi-firm homogeneous mass that is not grossly hemorrhagic.[6]

Tumor progression was observed after subcutaneous injection into the dorsal subcutis for 107 wild type, 129/Black Swiss mice. These mice were selected for their genetic background proximity to C57BL/6J mice. They observed the progression as being characterized by skin ulceration followed by ulcer hemorrhaging. Not only that, there was also basal hemorrhaging and/or edema.[4]

The cells were anaplastic, varying in size and shape; and they appeared to have little cytoplasm. The nuclei of the cells were highly distorted and prominent.[4]

The tumors were highly vascularized and metastasized to different sites, including the lungs, lymph nodes, liver, pleural cavity, diaphragm, pericardium, cardiac muscle, pancreas, adipose tissue, and esophagus. In cases of lung metastasis, large tumor masses underwent necrosis, with some of them hemorrhaging and even fewer exhibiting acute inflammation. Smaller metastases positioned themselves to be eccentric or concentric to vessels. In large tumor nodules, the cells grew, without patterning, into confluent sheets. The nodules had capillaries predominantly forming and supplying blood to the surface. The capillaries were fine and thin-walled. The nodules did exhibit expansion, interfering with and invading the space of surrounding tissues. This caused tissue degeneration.[4]


The Lewis lung carcinoma tumor model’s role in cancer has been its use for research into tumor metastasis and angiogenesis properties. The model is also useful for chemotherapeutic testing in vivo. Navelbine and carboplatin, two chemotherapeutics currently on the market, were tested in C57BL mice with Lewis lung carcinoma tumors in their hind flank. Tumor regression reached 72.7% in the navelbine trials, with the carboplatin trials showing that 30-50 percent of the population had a prolonged tumor survival after treatment with carboplatin and paclitaxel.[2]

Melittin, a polypeptide found in bee venom, on tumor-associated macrophages has been examined in a Lewis lung carcinoma model. Melittin has a background in research as a possible cancer drug due to its activity against malignant cells. Tumor-associated macrophages facilitate tumor progression through the promotion of angiogenesis and immunosuppression. In the in vivo tests, melittin inhibited rapid tumor growth and was correlated with decreased angiogenesis marker levels, VEGF and CD31.[7]

Toll-like receptor 4 mediates cancer-induced muscle wasting in a Lewis lung carcinoma model. It does so by directly activating muscle catabolism and stimulating an innate immune response in the mice.[8]

Targeting of CD169+ macrophages in order to inhibit tumor Lewis lung carcinoma growth also caused depletion of bone and bone marrow in mice. This depletion disrupted bone homeostasis and caused bone weight loss and a bone density decrease in mice. Not only that, erythropoietic activity was severely impaired. Therefore, the use of CD169+ macrophage targeting cancer therapies requires careful consideration of pitfalls.[9]

Cannabinoids suppress Lewis lung carcinoma cell growth. The mechanism of this action was shown to be inhibition of DNA synthesis[10] Cannabinoids increase the life span of mice carrying Lewis lung tumors and decrease primary tumor size.[11] There are multiple modes of action.[12]


  1. ^ Rashidi B, Yang M, Jiang P, Baranov E, An Z, Wang X, Moossa AR, Hoffman RM (2000-01-01). "A highly metastatic Lewis lung carcinoma orthotopic green fluorescent protein model". Clinical & Experimental Metastasis. 18 (1): 57–60. doi:10.1023/A:1026596131504. PMID 11206839. 
  2. ^ a b c Kellar A, Egan C, Morris D (2015). "Preclinical Murine Models for Lung Cancer: Clinical Trial Applications". BioMed Research International. 2015: 621324. doi:10.1155/2015/621324. PMID 26064932. 
  3. ^ Qiu W, Su GH (2013). "Development of orthotopic pancreatic tumor mouse models". Methods in Molecular Biology. 980: 215–23. doi:10.1007/978-1-62703-287-2_11. PMC 4049460Freely accessible. PMID 23359156. 
  4. ^ a b c d Bugge TH, Kombrinck KW, Xiao Q, Holmbäck K, Daugherty CC, Witte DP, Degen JL (December 1997). "Growth and dissemination of Lewis lung carcinoma in plasminogen-deficient mice". Blood. 90 (11): 4522–31. PMID 9373263. 
  5. ^ Anderson IC, Shipp MA, Docherty AJ, Teicher BA (February 1996). "Combination therapy including a gelatinase inhibitor and cytotoxic agent reduces local invasion and metastasis of murine Lewis lung carcinoma". Cancer Research. 56 (4): 715–8. PMID 8631001. 
  6. ^ Mayo JG (November 1972). "Biologic characterization of the subcutaneously implanted Lewis lung tumor". Cancer Chemotherapy Reports. Part 2. 3 (1): 325–30. PMID 4660735. 
  7. ^ Lee C, Bae SS, Joo H, Bae H (August 2017). "Melittin suppresses tumor progression by regulating tumor-associated macrophages in a Lewis lung carcinoma mouse model". Oncotarget. 8 (33): 54951–54965. doi:10.18632/oncotarget.18627. PMC 5589633Freely accessible. PMID 28903394. 
  8. ^ Zhang G, Liu Z, Ding H, Miao H, Garcia JM, Li YP (May 2017). "Toll-like receptor 4 mediates Lewis lung carcinoma-induced muscle wasting via coordinate activation of protein degradation pathways". Scientific Reports. 7 (1): 2273. doi:10.1038/s41598-017-02347-2. PMC 5442131Freely accessible. PMID 28536426. 
  9. ^ Jing W, Zhang L, Qin F, Li X, Guo X, Li Y, Qiu C, Zhao Y. "Targeting macrophages for cancer therapy disrupts bone homeostasis and impairs bone marrow erythropoiesis in mice bearing Lewis lung carcinoma tumors". Cellular Immunology. doi:10.1016/j.cellimm.2017.09.006. 
  10. ^ Friedman MA (1977). "In vivo effects of cannabinoids on macromolecular biosynthesis in Lewis lung carcinomas". Cancer Biochemistry Biophysics. 2 (2): 51–4. PMID 616322. 
  11. ^ Kogan NM (October 2005). "Cannabinoids and cancer". Mini Reviews in Medicinal Chemistry. 5 (10): 941–52. doi:10.2174/138955705774329555. PMID 16250836. 
  12. ^ Portella G, Laezza C, Laccetti P, De Petrocellis L, Di Marzo V, Bifulco M (September 2003). "Inhibitory effects of cannabinoid CB1 receptor stimulation on tumor growth and metastatic spreading: actions on signals involved in angiogenesis and metastasis". FASEB Journal. 17 (12): 1771–3. doi:10.1096/fj.02-1129fje. PMID 12958205.