The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Hedgehog signaling is restricted to the stromal compartment during pancreatic carcinogenesis
Open accessAbstract
The Hedgehog (Hh) pathway has been implicated in pancreatic cancer but its role remains controversial. To delineate the cell populations able to respond to Hh ligand stimulation, we expressed an oncogenic allele of Smoothened ( SmoM2 ) to cell autonomously activate Hh signaling in the mouse pancreas. Surprisingly, we found that expression of SmoM2 in epithelial cells was not able to activate the pathway and had no impact on pancreatic development or neoplasia. In contrast, activation of Smo in the mesenchyme led to Hh pathway activation, indicating that only the tumor stroma is competent to transduce the Hh signal. Using a Ptc-LacZ reporter mouse, we show that Hh signaling is active in stromal cells surrounding Hh-expressing tumor epithelium in various mouse pancreatic cancer models. Activation of the Hh pathway in the tumor stroma of human pancreatic and metastatic cancer specimens was confirmed by quantitative RT-PCR of microdissected tissue samples. These data support a paracrine model of Hh-mediated tumorigenesis, in which tumor cells secrete Hh ligand to induce tumor-promoting Hh target genes in adjacent stroma.
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Cites
Altered Neural Cell Fates and Medulloblastoma in Mouse patched Mutants
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Vertebrate Smoothened functions at the primary cilium
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Notch mediates TGFα-induced changes in epithelial differentiation during pancreatic tumorigenesis
Miyamoto, Y., Maitra, A., Ghosh, B., Zechner, U., Argani, P., Iacobuzio-Donahue, C. A., Sriuranpong, V., Iso, T., Meszoely, I. M., Wolfe, M. S., et al. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00140-5 · Cited by 643
Hedgehog signaling and primary cilia are required for the formation of adult neural stem cells
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Cited by
Olive, K. P., Jacobetz, M. A., Davidson, C. J., Gopinathan, A., McIntyre, D., Honess, D., Madhu, B., Goldgraben, M. A., Caldwell, M. E., Allard, D., et al. (2009) · Science · doi:10.1126/science.1171362 · Cited by 3,170
Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer
Öhlund, D., Handly-Santana, A., Biffi, G., Elyada, E., Almeida, A. S., Ponz-Sarvise, M., Corbo, V., Oni, T. E., Hearn, S. A., Lee, E. J., et al. (2017) · Journal of Experimental Medicine · doi:10.1084/jem.20162024 · Cited by 2,590
Stromal Elements Act to Restrain, Rather Than Support, Pancreatic Ductal Adenocarcinoma
Rhim, A. D., Oberstein, P. E., Thomas, D. H., Mirek, E. T., Palermo, C. F., Sastra, S. A., Dekleva, E. N., Saunders, T., Becerra, C. P., Tattersall, I. W., et al. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.04.021 · Cited by 2,085
The Pancreas Cancer Microenvironment
Feig, C., Gopinathan, A., Neesse, A., Chan, D. S., Cook, N., & Tuveson, D. A. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-3114 · Cited by 1,316
Hyaluronan impairs vascular function and drug delivery in a mouse model of pancreatic cancer
Jacobetz, M. A., Chan, D. S., Neesse, A., Bapiro, T. E., Cook, N., Frese, K. K., Feig, C., Nakagawa, T., Caldwell, M. E., Zecchini, H. I., et al. (2013) · Gut · doi:10.1136/gutjnl-2012-302529 · Cited by 1,120
Metadata
- Authors
- Tian, H., Callahan, C. A., DuPree, K. J., Darbonne, W. C., Ahn, C. P., Scales, S. J., & de Sauvage, F. J.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2009-03-17
- Volume
- 106
- Issue
- 11
- Pages
- 4254-4259
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2079067257
- Cited by
- 404
- References
- 7
- FWCI
- 17.40
- Type
- journal article
- Language
- en
- Open access
- green
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- Tian, H., Callahan, C. A., DuPree, K. J., Darbonne, W. C., Ahn, C. P., Scales, S. J., & de Sauvage, F. J. (2009). Hedgehog signaling is restricted to the stromal compartment during pancreatic carcinogenesis. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0813203106
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