The site of the Media Sphera Publishers contains materials intended solely for healthcare professionals.
By closing this message, you confirm that you are a certified medical professional or a student of a medical educational institution.

Login
EN
+7 (495) 482-4118
+7 (495) 482-4329
+8 800 250-18-12
  • (toll-free number for subscriptions)
    Mon-Fri from 10 a.m. to 6 p.m.

  • © 1998-2025
+7 (495) 482-43-29
EN
All journals
Journal
Year
Year
Search result: 0

Kuznetsova A.V.

A.I. Evdokimov Moscow State University of Medicine and Dentistry;
N.K. Koltsov Institute of Developmental Biology

Popova O.P.

A.I. Evdokimov Moscow State University of Medicine and Dentistry

Astakhov D.A.

A.I. Evdokimov Moscow State University of Medicine and Dentistry

Ivanov Yu.V.

A.I. Evdokimov Moscow State University of Medicine and Dentistry

Panchenkov D.N.

A.I. Evdokimov Moscow State University of Medicine and Dentistry

Ivanov A.A.

A.I. Evdokimov Moscow State University of Medicine and Dentistry

Epithelial-stromal interactions in pancreatic adenocarcinoma: the role of stroma in disease progression

Authors:

Kuznetsova A.V., Popova O.P., Astakhov D.A., Ivanov Yu.V., Panchenkov D.N., Ivanov A.A.

More about the authors

Journal: Russian Journal of Archive of Pathology. 2022;84(5): 65‑70

DOI: 10.17116/patol20228405165

Read: 3007 times

Download PDF (RU)
Contact the author
Table of contents

EPITHELIAL-STROMAL INTERACTIONS IN PANCREATIC ADENOCARCINOMA: THE ROLE OF STROMA IN DISEASE PROGRESSION
EPITHELIAL-STROMAL INTERACTIONS IN PANCREATIC ADENOCARCINOMA: THE ROLE OF STROMA IN DISEASE PROGRESSION

To cite this article:

Kuznetsova AV, Popova OP, Astakhov DA, Ivanov YuV, Panchenkov DN, Ivanov AA. Epithelial-stromal interactions in pancreatic adenocarcinoma: the role of stroma in disease progression. Russian Journal of Archive of Pathology. 2022;84(5):65‑70. (In Russ.)
https://doi.org/10.17116/patol20228405165

Подписка 2026 Архив патологии (Russian Journal of Archive of Pathology)
МСФ на ЯМ
Использование инфографики авторами научных работ
Close metadata
Recommended articles:
Patterns of CAF expression in tumors of the geni­tourinary system. Russian Journal of Archive of Pathology. 2024;(6):28-35
The impact of combined immu­notherapy on the cellular composition of the tumor microenvironment in patients with gastric carcinoma. Russian Journal of Archive of Pathology. 2025;(4):24-30
Characteristics of the immune microenvironment of endo­metrial cancer depe­nding on the MMR status of the tumor. Russian Journal of Archive of Pathology. 2025;(5):11-19
Abstract:

Pancreatic ductal adenocarcinoma (PDAC) is the most common and difficult to treat form of pancreas cancer. PDAC and other solid cancers contain both tumor cells and normal connective tissue cells called stromal cells, which are responsible for the excess production of extracellular matrix. It is known that in more than 90% of PDAC tumors and in many other types of cancer, mutations of the KRAS gene are observed, the reciprocal signaling of which has been shown between tumor and stromal cells in vitro. Pancreatic stromal stellate cells are considered precursors of activated or tumor-associated fibroblasts (CAFs), which are an increasing population of cells that proliferate in situ or are recruited into the tumor. CAFs are a heterogeneous population of stromal fibroblasts with different molecular profiles that change during tumorigenesis. Both immunosuppressive and immunosuppressive subsets of CAFs can coexist in the stroma of a single tumor. Based on the heterogeneity of the intertumor stroma, attempts are being made to classify PDAC and predict the course of the disease.

Keywords:

pancreatic ductal adenocarcinoma
PDAC
tumor microenvironment
cancer-associated fibroblasts
CAFs
inter-tumor stroma

Authors:

Kuznetsova A.V.

A.I. Evdokimov Moscow State University of Medicine and Dentistry;
N.K. Koltsov Institute of Developmental Biology

Popova O.P.

A.I. Evdokimov Moscow State University of Medicine and Dentistry

Astakhov D.A.

A.I. Evdokimov Moscow State University of Medicine and Dentistry

Ivanov Yu.V.

A.I. Evdokimov Moscow State University of Medicine and Dentistry

Panchenkov D.N.

A.I. Evdokimov Moscow State University of Medicine and Dentistry

Ivanov A.A.

A.I. Evdokimov Moscow State University of Medicine and Dentistry

Received:

27.04.2022

Accepted:

22.06.2022

Close metadata

References:

  1. Raphael BJ, Hruban RH, Aguirre AJ, Moffitt RA, Yeh JJ, Stewart C, Robertson AG, Cherniack AD, Gupta M, Getz G, et al. Integrated genomic characterization of pancreatic ductal adenocarcinoma. Cancer Cell. 2017;32(2):185-203.e13.  https://doi.org/10.1016/j.ccell.2017.07.007
  2. Kotoula V, Charalambous E, Biesmans B, Malousi A, Vrettou E, Fountzilas G, Karkavelas G. Targeted KRAS mutation assessment on patient tumor histologic material in real time diagnostics. PLoS One. 2009;4(11):e7746. https://doi.org/10.1371/journal.pone.0007746
  3. Avery JT, Zhang R, Boohaker RJ. GLI1: a therapeutic target for cancer. Front Oncol. 2021;11:673154. https://doi.org/10.3389/fonc.2021.673154
  4. Maitra A, Hruban RH. Pancreatic cancer. Annu Rev Pathol. 2008;3:157-88.  https://doi.org/10.1146/annurev.pathmechdis.3.121806.154305
  5. Tape CJ, Ling S, Dimitriadi M, McMahon KM, Worboys JD, Leong HS, Norrie IC, Miller CJ, Poulogiannis G, Lauffenburger DA, Jørgensen C. Oncogenic KRAS regulates tumor cell signaling via stromal reciprocation. Cell. 2016;165(4):910-920.  https://doi.org/10.1016/j.cell.2016.03.029
  6. Kamerkar S, Lebleu VS, Sugimoto H, Yang S, Ruivo CF, Melo SA, Lee JJ, Kalluri R. Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer. Nature. 2017;546(7659):498-503.  https://doi.org/10.1038/nature22341
  7. Buscail L, Bournet B, Cordelier P. Role of oncogenic KRAS in the diagnosis, prognosis and treatment of pancreatic cancer. Nat Rev Gastroenterol Hepatol. 2020;17(3):153-68.  https://doi.org/10.1038/s41575-019-0245-4
  8. Bachem MG, Zhou S, Buck K, Schneiderhan W, Siech M. Pancreatic stellate cells — role in pancreas cancer. Langenbecks Arch Surg. 2008;393(6):891-900.  https://doi.org/10.1007/s00423-008-0279-5
  9. Maeda K, Enomoto A, Hara A, Asai N, Kobayashi T, Horinouchi A, Maruyama S, Ishikawa Y, Nishiyama T, Kiyoi H, et al. Identification of Meflin as a potential marker for mesenchymal stromal cells. Sci Rep. 2016;6:22288. https://doi.org/10.1038/srep22288
  10. Takahashi M, Kobayashi H, Mizutani Y, Hara A, Iida T, Miyai Y, Asai N, Enomoto A. Roles of the mesenchymal stromal/stem cell marker Meflin/Islr in cancer fibrosis. Front Cell Dev Biol. 2021;9:749924. https://doi.org/10.3389/fcell.2021.749924
  11. Mizutani Y, Kobayashi H, Iida T, Asai N, Masamune A, Hara A, Esaki N, Ushida K, Mii S, Shiraki Y, et al. Meflin-positive cancer-associated fibroblasts inhibit pancreatic carcinogenesis. Cancer Res. 2019;79(20):5367-5381. https://doi.org/10.1158/0008-5472.CAN-19-0454
  12. LeBleu VS, Kalluri R. A peek into cancer-associated fibroblasts: origins, functions and translational impact. Dis Model Mech. 2018;11(4):dmm029447. https://doi.org/10.1242/dmm.029447
  13. Kalluri R. The biology and function of fibroblasts in cancer. Nat Rev Cancer. 2016;16(9):582-598.  https://doi.org/10.1038/nrc.2016.73
  14. Helms EJ, Berry MW, Chaw RC, Dufort CC, Sun D, Onate MK, Oon C, Bhattacharyya S, Sanford-Crane H, Horton W, et al. Mesenchymal lineage heterogeneity underlies nonredundant functions of pancreatic cancer—associated fibroblasts. Cancer Discov. 2022;12(2):484-501.  https://doi.org/10.1158/2159-8290.CD-21-0601
  15. Shiga K, Hara M, Nagasaki T, Sato T, Takahashi H, Takeyama H. Cancer-associated fibroblasts: their characteristics and their roles in tumor growth. Cancers (Basel). 2015;7(4):2443-2458. https://doi.org/10.3390/cancers7040902
  16. Potenta S, Zeisberg E, Kalluri R. The role of endothelial-to-mesenchymal transition in cancer progression. Br J Cancer. 2008;99(9):1375-1379. https://doi.org/10.1038/sj.bjc.6604662
  17. Kalluri R, Weinberg RA. The basics of epithelial-mesenchymal transition. J Clin Invest. 2009;119(6):1420-1428. https://doi.org/10.1172/JCI39104
  18. Öhlund D, Handly-Santana A, Biffi G, Elyada E, Almeida AS, Ponz-Sarvise M, Corbo V, Oni TE, Hearn SA, Lee EJ, et al. Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer. J Exp Med. 2017;214(3):579-596.  https://doi.org/10.1084/jem.20162024
  19. Elyada E, Bolisetty M, Laise P, Flynn WF, Courtois ET, Burkhart RA, Teinor JA, Belleau P, Biffi G, Lucito MS, et al. Cross-species single-cell analysis of pancreatic ductal adenocarcinoma reveals antigen-presenting cancer-associated fibroblasts. Cancer Discov. 2019;9(8):1102-1123. https://doi.org/10.1158/2159-8290.CD-19-0094
  20. Neuzillet C, Tijeras-Raballand A, Ragulan C, Cros J, Patil Y, Martinet M, Erkan M, Kleeff J, Wilson J, Apte M, et al. Inter- and intra-tumoural heterogeneity in cancer-associated fibroblasts of human pancreatic ductal adenocarcinoma. J Pathol. 2019;248(1):51-65.  https://doi.org/10.1002/path.5224
  21. De Jaeghere EA, Denys HG, De Wever O. Fibroblasts fuel immune escape in the tumor microenvironment. Trends Cancer. 2019;5(11):704-723.  https://doi.org/10.1016/j.trecan.2019.09.009
  22. Biffi G, Oni TE, Spielman B, Hao Y, Elyada E, Park Y, Preall J, Tuveson DA. Il1-induced JAK/STAT signaling is antagonized by TGFβ to shape CAF heterogeneity in pancreatic ductal adenocarcinoma. Cancer Discov. 2019;9(2):282-301.  https://doi.org/10.1158/2159-8290.CD-18-0710
  23. Bernard V, Semaan A, Huang J, San Lucas FA, Mulu FC, Stephens BM, Guerrero PA, Huang Y, Zhao J, Kamyabi N, et al. Single-cell transcriptomics of pancreatic cancer precursors demonstrates epithelial and microenvironmental heterogeneity as an early event in neoplastic progression. Clin Cancer Res. 2019;25(7):2194-2205. https://doi.org/10.1158/1078-0432.CCR-18-1955
  24. Avery D, Govindaraju P, Jacob M, Todd L, Monslow J, Puré E. Extracellular matrix directs phenotypic heterogeneity of activated fibroblasts. Matrix Biol. 2018;67:90-106.  https://doi.org/10.1016/j.matbio.2017.12.003
  25. Feig C, Jones JO, Kraman M, Wells RJB, Deonarine A, Chan DS, Connell CM, Roberts EW, Zhao Q, Caballero OL, et al. Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer. Proc Natl Acad Sci USA. 2013;110(50):20212-20217. https://doi.org/10.1073/pnas.1320318110
  26. McAndrews KM, Chen Y, Darpolor JK, Zheng X, Yang S, Carstens JL, Li B, Wang H, Miyake T, Correa de Sampaio P, et al. Identification of functional heterogeneity of carcinoma-associated fibroblasts with distinct IL6-mediated therapy resistance in pancreatic cancer. Cancer Discov. 2022;12(6):1580-1597. https://doi.org/10.1158/2159-8290.cd-20-1484
  27. Rhim AD, Oberstein PE, Thomas DH, Mirek ET, Palermo CF, Sastra SA, Dekleva EN, Saunders T, Becerra CP, Tattersall IW, et al. Stromal elements act to restrain, rather than support, pancreatic ductal adenocarcinoma. Cancer Cell. 2014;25(6):735-747.  https://doi.org/10.1016/j.ccr.2014.04.021
  28. Özdemir BC, Pentcheva-Hoang T, Carstens JL, Zheng X, Wu CC, Simpson TR, Laklai H, Sugimoto H, Kahlert C, Novitskiy SV, et al. Depletion of carcinoma-associated fibroblasts and fibrosis induces immunosuppression and accelerates pancreas cancer with reduced survival. Cancer Cell. 2014;25(6):719-734.  https://doi.org/10.1016/j.ccr.2014.04.005
  29. Chen Y, Kim J, Yang S, Wang H, Wu CJ, Sugimoto H, LeBleu VS, Kalluri R. Type I collagen deletion in αSMA+ myofibroblasts augments immune suppression and accelerates progression of pancreatic cancer. Cancer Cell. 2021;39(4):548-565.e6.  https://doi.org/10.1016/j.ccell.2021.02.007
  30. Jiang H, Torphy RJ, Steiger K, Hongo H, Ritchie AJ, Kriegsmann M, Horst D, Umetsu SE, Joseph NM, McGregor K, et al. Pancreatic ductal adenocarcinoma progression is restrained by stromal matrix. J Clin Invest. 2020;130(9):4704-4709. https://doi.org/10.1172/JCI136760
  31. Torphy RJ, Wang Z, True-Yasaki A, Volmar KE, Rashid N, Yeh B, Johansen JS, Hollingsworth MA, Yeh JJ, Collisson EA. Stromal content is correlated with tissue site, contrast retention, and survival in pancreatic adenocarcinoma. JCO Precis Oncol. 2018;2018:PO.17.00121. https://doi.org/10.1200/po.17.00121
  32. Brock A, Krause S, Ingber DE. Control of cancer formation by intrinsic genetic noise and microenvironmental cues. Nat Rev Cancer. 2015;15(8):499-509.  https://doi.org/10.1038/nrc3959
  33. Sherman MH, Yu RT, Engle DD, Ding N, Atkins AR, Tiriac H, Collisson EA, Connor F, Van Dyke T, Kozlov S, et al. Vitamin D receptor-mediated stromal reprogramming suppresses pancreatitis and enhances pancreatic cancer therapy. Cell. 2014;159(1):80-93.  https://doi.org/10.1016/j.cell.2014.08.007
  34. Jaster R. Molecular regulation of pancreatic stellate cell function. Mol Cancer. 2004;3:26.  https://doi.org/10.1186/1476-4598-3-26
  35. Collisson EA, Sadanandam A, Olson P, Gibb WJ, Truitt M, Gu S, Cooc J, Weinkle J, Kim GE, Jakkula L, et al. Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy. Nat Med. 2011;17(4):500-503.  https://doi.org/10.1038/nm.2344
  36. Moffitt RA, Marayati R, Flate EL, Volmar KE, Loeza SGH, Hoadley KA, Rashid NU, Williams LA, Eaton SC, Chung AH, et al. Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma. Nat Genet. 2015;47(10):1168-1178. https://doi.org/10.1038/ng.3398
  37. Bailey P, Chang DK, Nones K, Johns AL, Patch AM, Gingras MC, Miller DK, Christ AN, Bruxner TJC, Quinn MC, et al. Genomic analyses identify molecular subtypes of pancreatic cancer. Nature. 2016;531(7592):47-52.  https://doi.org/10.1038/nature16965
  38. Puleo F, Nicolle R, Blum Y, Cros J, Marisa L, Demetter P, Quertinmont E, Svrcek M, Elarouci N, Iovanna J, et al. Stratification of pancreatic ductal adenocarcinomas based on tumor and microenvironment features. Gastroenterology. 2018;155(6):1999-2013.e3.  https://doi.org/10.1053/j.gastro.2018.08.033
  39. O’Kane GM, Grunwald BT, Jang GH, Masoomian M, Picardo S, Grant RC, Denroche RE, Zhang A, Wang Y, Lam B, et al. GATA6 expression distinguishes classical and basal-like subtypes in advanced pancreatic cancer. Clin Cancer Res. 2020;26(18):4901-4910. https://doi.org/10.1158/1078-0432.CCR-19-3724
  40. Wang X, Li L, Yang Y, Fan L, Ma Y, Mao F. Reveal the heterogeneity in the tumor microenvironment of pancreatic cancer and analyze the differences in prognosis and immunotherapy responses of distinct immune subtypes. Front Oncol. 2022;12:832715. https://doi.org/10.3389/fonc.2022.832715
Contact the author
Email
Message
The publishing house "Media Sphere" does not provide treatment services, does not give recommendations on contacting medical institutions and specific specialists, on the prescription of medicines and dietary supplements.

Email Confirmation

An email was sent to test@gmail.com with a confirmation link. Follow the link from the letter to complete the registration on the site.

Email Confirmation

Contact us
If you have any questions, complaints or suggestions, please use this feedback form.
Email
Message
The publishing house "Media Sphere" does not provide treatment services, does not give recommendations on contacting medical institutions and specific specialists, on the prescription of medicines and dietary supplements.
Submit Application

You can become an author of one of our magazines, send a request and we will consider it in during the day.

Name
Phone
E-mail
Message
Login
Registration
E-mail
Password
Forgot Password?

Log in to the site using your account in one of the services

Password recovery
E-mail
Login
Register

We use cооkies to improve the performance of the site. By staying on our site, you agree to the terms of use of cооkies. To view our Privacy and Cookie Policy, please. click here.