Helminth-derived molecules inhibit colitis-associated colon cancer development through NF-κB and STAT3 regulation
Blanca E. Callejas
Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México, Mexico
Search for more papers by this authorMónica G. Mendoza-Rodríguez
Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México, Mexico
Search for more papers by this authorOlga Villamar-Cruz
Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México, Mexico
Search for more papers by this authorSandy Reyes-Martínez
Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México, Mexico
Search for more papers by this authorCuauhtémoc Angel Sánchez-Barrera
Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México, Mexico
Search for more papers by this authorMiriam Rodríguez-Sosa
Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México, Mexico
Search for more papers by this authorNorma L. Delgado-Buenrostro
Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México, Mexico
Search for more papers by this authorDiana Martínez-Saucedo
Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México, Mexico
Search for more papers by this authorYolanda I. Chirino
Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México, Mexico
Search for more papers by this authorSonia A. León-Cabrera
Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México, Mexico
Search for more papers by this authorCarlos Pérez-Plasencia
Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México, Mexico
Subdirección de Investigación Básica, Instituto Nacional de Cancerología, Ciudad de México, Mexico
Search for more papers by this authorFelipe Vaca-Paniagua
Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México, Mexico
Subdirección de Investigación Básica, Instituto Nacional de Cancerología, Ciudad de México, Mexico
Laboratorio Nacional en Salud, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México, Mexico
Search for more papers by this authorLuis E. Arias-Romero
Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México, Mexico
Search for more papers by this authorCorresponding Author
Luis I. Terrazas
Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México, Mexico
Laboratorio Nacional en Salud, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México, Mexico
Correspondence to: Luis I. Terrazas, Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tel.: +52-55-5623-1333, ext. 39773, E-mail: [email protected]Search for more papers by this authorBlanca E. Callejas
Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México, Mexico
Search for more papers by this authorMónica G. Mendoza-Rodríguez
Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México, Mexico
Search for more papers by this authorOlga Villamar-Cruz
Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México, Mexico
Search for more papers by this authorSandy Reyes-Martínez
Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México, Mexico
Search for more papers by this authorCuauhtémoc Angel Sánchez-Barrera
Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México, Mexico
Search for more papers by this authorMiriam Rodríguez-Sosa
Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México, Mexico
Search for more papers by this authorNorma L. Delgado-Buenrostro
Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México, Mexico
Search for more papers by this authorDiana Martínez-Saucedo
Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México, Mexico
Search for more papers by this authorYolanda I. Chirino
Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México, Mexico
Search for more papers by this authorSonia A. León-Cabrera
Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México, Mexico
Search for more papers by this authorCarlos Pérez-Plasencia
Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México, Mexico
Subdirección de Investigación Básica, Instituto Nacional de Cancerología, Ciudad de México, Mexico
Search for more papers by this authorFelipe Vaca-Paniagua
Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México, Mexico
Subdirección de Investigación Básica, Instituto Nacional de Cancerología, Ciudad de México, Mexico
Laboratorio Nacional en Salud, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México, Mexico
Search for more papers by this authorLuis E. Arias-Romero
Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México, Mexico
Search for more papers by this authorCorresponding Author
Luis I. Terrazas
Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México, Mexico
Laboratorio Nacional en Salud, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México, Mexico
Correspondence to: Luis I. Terrazas, Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tel.: +52-55-5623-1333, ext. 39773, E-mail: [email protected]Search for more papers by this authorAbstract
Inflammation is currently considered a hallmark of cancer and plays a decisive role in different stages of tumorigenesis, including initiation, promotion, progression, metastasis and resistance to antitumor therapies. Colorectal cancer is a disease widely associated with local chronic inflammation. Additionally, extrinsic factors such as infection may beneficially or detrimentally alter cancer progression. Several reports have noted the ability of various parasitic infections to modulate cancer development, favoring tumor progression in many cases and inhibiting tumorigenesis in others. The aim of our study was to determine the effects of excreted/secreted products of the helminth Taenia crassiceps (TcES) as a treatment in a murine model of colitis-associated colon cancer (CAC). Here, we found that after inducing CAC, treatment with TcES was able to reduce inflammatory cytokines such as IL-1β, TNF-α, IL-33 and IL-17 and significantly attenuate colon tumorigenesis. This effect was associated with the inhibition of signal transducer and activator of transcription 3 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) phosphorylation. Furthermore, we determined that TcES interfered with LPS-induced NF-κB p65 activation in human colonic epithelial cell lines in a Raf-1 proto-oncogene-dependent manner. Moreover, in three-dimensional cultures, TcES promoted reorganization of the actin cytoskeleton, altering cell morphology and forming colonospheres, features associated with a low grade of aggressiveness. Our study demonstrates a remarkable effect of helminth-derived molecules on suppressing ongoing colorectal cancer by downregulating proinflammatory and protumorigenic signaling pathways.
Abstract
What's new?
Worm infections usually cause unwanted gastrointestinal diseases, but their effects on colorectal cancer development remain unclear. Here the authors demonstrate a notable anti-tumor effect of molecules derived from Taenia crassiceps (TcES), a tapeworm found in wolves. The secreted molecules downregulated proinflammatory and protumorigenic signaling, such as that mediated by STAT3, AKT and NF-kappaB, underscoring the role of inflammation in colorectal tumorigenesis and pointing to potential therapeutic implications of helminth-derived molecules.
Open Research
Data availability
The data will be made available upon reasonable request.
Supporting Information
| Filename | Description |
|---|---|
| ijc32626-sup-0001-FigureS1.docxWord 2007 document , 33.8 KB | Supplementary Fig 1 Cytokines at different times of development of the CAC. a) IL-1β, b) IL-10 c) IL-6 concentrations in supernatants of colon culture on days 26, 47, and 68 after AOM/DSS induction were measured by ELISA. The results are representative of four independent experiments and expressed as the mean ± SE *** P < 0.0001 ** P < 0.01 *P < 0.05. |
| ijc32626-sup-0002-FigureS2.docxWord 2007 document , 338.6 KB | Supplementary Fig. 2 Cytokines in spleen and inflammatory monocytes in blood circulation a) TNF-α, b) IL-10 concentrations in spleen culture stimulated or not with α-CD3 after AOM/DSS induction were measured by ELISA c) Analysis strategy d) Representative flow cytometry plots from control mice, CAC mice and CAC + TcES mice gated on CD11b+ living cells isolated from the circulation. Percentage of e) CD11b+Ly6ChiCCR2+ cells and IMF of f) CCR2. Data are representative of four independent experiments. Values are mean ± SE *** P < 0.0001 ** P < 0.01 * P < 0.05. |
| ijc32626-sup-0003-TableS1.docxWord 2007 document , 14.9 KB | Supplementary Table 1 Primer sequences for qPCR analysis. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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