OncologyColorectal cancer laboratory

Unraveling Cancer Stem Cells and the Origins of Metastasis

Colorectal cancer laboratory
<p>Batlle</p>
Group Leader

ICREA Research Professor, ERC Advanced Grant

+34 93 40 39008

Colorectal cancer (CRC) is the most frequent and the second-most deadly type of cancer with around 700,000 deaths worldwide. Most colorectal tumors develop as benign lesions but a small proportion progress to more malignant stages when the appropriate alterations in oncogenes and tumour suppressor genes occur. The final and deadliest step in colorectal cancer progression is the metastatic dissemination of CRC cells to foreign organs such as the liver and the lungs.

Our lab studies the evolution of intestinal stem cells and their ecosystem during cancer progression, with a particular interests in unraveling how the tumor microenvironment facilitates immune evasion and metastasis. The ultimate goal is to obtain information that help design new therapeutic and diagnostic tools.

1. Connecting stem cells to colorectal cancer
Tissues such as the intestinal epithelium and the hematopoietic system continuously self-renew through the activity of a dedicated population of tissue-specific stem cells. Unlike the bulk of the cells that populate these tissues, adult stem cells are long-lived and generate cellular progeny throughout life to regenerate the multiple specialized, short-lived cells that ultimately perform tissue-specific functions. The cancer stem cell (CSCs) theory states that tumor growth is similarly fueled by small numbers of tumor stem cells hidden in cancers. It explains clinical obser¬vations, such as the almost inevitable recurrence of tumors after initially successful chemotherapy and/or radiation therapy, the phenomenon of tumor dormancy, and metastasis. Our laboratory pioneers the notion that colorectal cancers retain a cell hierarchy similar to that of the normal intestinal mucosa. We have characterized extensively tumor stem cell population in CRCs and its role in chemotherapy resistance and relapse. We are currently pursuing the following questions:

- How does the tumor niche specify the CSC state?
- To which extent are tumor-cell phenotypes reversible or interchangeable?
- What type of ‘regenerative’ responses occur upon CSC loss in a tumor, and how are these controlled?
- Which are the intermedi¬ate states adopted by tumor cells during invasion?
- How metabolic states of tumor stem cells controlled, and what are their effects?

 

2. Tumor microenvironment, immune evasion and metastasis
A large proportion of deaths by colorectal cancer are the consequence of metastasis. This process involves the regeneration of a full-blown tumor from disseminated cancer cells and it is intrinsically inefficient mainly due to the inability of isolated tumor cells to colonize host tissues and reinitiate tumor growth in a different environment. The most accepted view is that competences to overcome this bottleneck result from clonal selection of appropriate genetic alterations in cancer cells. However, primary CRCs and metastases do not differ significantly in their mutational content and none of the main alterations in driver oncogenes and tumor suppressor genes correlate significantly with patient outcome. Our laboratory recently discovered that the key genetic programs associated to poor prognosis in CRC patients are expressed in cells of the tumor microenvironment (TME). TGF-beta signaling is the main architect of the TME in metastatic CRC and appears to help metastatic cancer cells evade the immune system. This finding opens up the development of new therapeutic and diagnostic tools for advanced CRC patients based on targeting the TME. Key questions and research lines in this area include:

- Why some CRCs develop a TGF-beta-activated TME and others don’t?
- How cancer associated fibroblasts mediate the phenomenon of immune exclusion?
- Genetic analysis of the metastatic niche.
- Study the immunology of residual disease. How systemic factors influence cancer recurrence?

Tauriello DVF, Palomo-Ponce S, Stork D, Berenguer-Llergo A, Badia-Ramentol J, Iglesias M, Sevillano M, Ibiza S, Cañellas A, Hernando-Momblona X, Byrom D, Matarin JA, Calon A, Rivas EI, Nebreda AR, Riera A, Attolini CS and Batlle E.
Nature, 554 (7693), 538-543 (2018)
Batlle E and Clevers H.
Nat Med, 23 (10), 1124-1134 (2017)
Cortina C, Turon G, Stork D, Hernando-Momblona X, Sevillano M, Aguilera M, Tosi S, Merlos-Suárez A, Stephan-Otto Attolini C, Sancho E and Batlle E.
EMBO Mol Med, (2017)
Barriga FM, Montagni E, Mana M, Mendez-Lago M, Hernando-Momblona X, Sevillano M, Guillaumet-Adkins A, Rodriguez-Esteban G, Buczacki SJA, Gut M, Heyn H, Winton DJ, Yilmaz OH, Attolini CS, Gut I and Batlle E.
Cell Stem Cell, 20 (6), 801-816.e7 (2017)
Calon A, Lonardo E, Berenguer-Llergo A, Espinet E, Hernando-Momblona X, Iglesias M, Sevillano M, Palomo-Ponce S, Tauriello DV, Byrom D, Cortina C, Morral C, Barceló C, Tosi S, Riera A, Attolini CS, Rossell D, Sancho E and Batlle E.
Nat Genet, 47 (4), 320-329 (2015)
Oskarsson T, Batlle E and Massagué J.
Cell Stem Cell, 14 (3), 306-21 (2014)
Whissell G, Montagni E, Martinelli P, Hernando-Momblona X, Sevillano M, Jung P, Cortina C, Calon A, Abuli A, Castells A, Castellvi-Bel S, Nacht AS, Sancho E, Stephan-Otto Attolini C, Vicent GP, Real FX and Batlle E.
Nat Cell Biol, 16 (7), 695-707 (2014)
Urosevic J, Garcia-Albéniz X, Planet E, Real S, Céspedes MV, Guiu M, Fernandez E, Bellmunt A, Gawrzak S, Pavlovic M, Mangues R, Dolado I, Barriga FM, Nadal C, Kemeny N, Batlle E, Nebreda AR and Gomis RR.
Nat Cell Biol, 16 (7), 685-94 (2014)
Calon A, Espinet E, Palomo-Ponce S, Tauriello DV, Iglesias M, Céspedes MV, Sevillano M, Nadal C, Jung P, Zhang XH, Byrom D, Riera A, Rossell D, Mangues R, Massagué J, Sancho E and Batlle E.
Cancer Cell, 22 (5), 571-84 (2012)
Campbell K, Whissell G, Franch-Marro X, Batlle E and Casanova J.
Dev Cell, 21 (6), 1051-61 (2011)
Jung P, Sato T, Merlos-Suárez A, Barriga FM, Iglesias M, Rossell D, Auer H, Gallardo M, Blasco MA, Sancho E, Clevers H and Batlle E.
Nat Med, 17 (10), 1225-7 (2011)
Solanas G, Cortina C, Sevillano M and Batlle E.
Nat Cell Biol, 13 (9), 1100-7 (2011)
Merlos-Suárez A, Barriga FM, Jung P, Iglesias M, Céspedes MV, Rossell D, Sevillano M, Hernando-Momblona X, da Silva-Diz V, Muñoz P, Clevers H, Sancho E, Mangues R and Batlle E.
Cell Stem Cell, 8 (5), 511-24 (2011)

This group receives financial support from the following sources:

  • Ministerio de Educación y Ciencia (Spanish Ministry of Science and Education)
  • Generalitat de Catalunya (DURSI) (Government of Catalonia) 
  • SuppresSTEM consortium
  • Ministerio de Economía y Competitividad (MINECO)
  • European Commission (EC), Fondo Europeo de Desarrollo Regional (FEDER), "Una manera de hacer Europa"

     

Group news & mentions

<p>Eduard Batlle, head of the Colorectal Cancer laboratory at IRB Barcelona</p>
31 May 2018

The Heraldo newspaper has published an article about the role of immunotherapy to rearm patients’ defences and contribute to the fight against cancer.

<p>Presentation of Gemma Turon. Image: El Periódico</p>
15 May 2018

El Periódico newspaper has published an article about “Pint of Science”, a science festival that took place on Monday at the same time and in different bars around the city of Barcelona.

<p>Eduard Battle with the members of the Colorectal Cancer Lab at IRB Barcelona</p>
10 Apr 2018

This afternoon, Eduard Batlle, head of the Colorectal Cancer Lab at the Institute for Research in Biomedicine (IRB Barcelona), is to be presented with the XIV Medal from the Fu

<p>Eduard Batlle, head of the Colorectal Cancer laboratory at IRB Barcelona</p>
4 Apr 2018

The website SelectScience has published an article about research headed by Eduard Batlle, head of the Colorectal Cancer Lab at IRB Barcelona, on the effectiveness of treatments that enhance immune

Upcoming events

28 Jun
Fèlix Serratosa Room, Parc Científic de Barcelona
Speaker:
Jorge Cordero, Nerea Sánchez, Laura Tiessler and Sara Vives