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Tumor-microenvironment interactions in gastrointestinal cancer - Marco Gerling

Cancer cells are highly susceptible to influences from their microenvironment.
Our group studies tumor-microenvironment interactions to understand how cellular crosstalk shapes tumor progression and metastases.

Immunofluorescence staining of mouse colon with CD49f (green), ASMA (blue), with tdTomato (of Col1a2CreER;R26-LSL-tdTomato mice, red), and DAPI (nuclear stain, grey).

Colorectal and Pancreatic Cancer

Taken together, colorectal cancer and pancreatic ductal adenocarcinoma account for more than 5000 new cancer cases per year in Sweden alone. Both tumor types arise from epithelial cells of the gastrointestinal tract and show overlapping alterations in key signaling pathways, acting through paracrine feedback via the microenvironment. To understand how cancer cells from these types of tumors interact with their microenvironment, we use advanced genetic mouse models and ex vivo cell culture systems. Importantly, we can rely on a different cohorts of patient samples from national and international collaborations to relate our functional findings to human disease.

Our goal is to bridge clinical practice and basic research in order to uncover ways to exploit cellular interactions for cancer therapy.

Liver metastasis of pancreatic cancer in a murine liver; image taken by Rosan Heijboer.

Liver Metastases

When tumor cells metastasize to distant organs, they meet entirely new interaction partners. Most metastases of gastrointestinal cancers are found in the liver, where tumor cells meet a multitude of novel cell types, including hepatocytes, hepatic stellate cells, Kupffer cells, as well as a distinct immune cell infiltrate. However, very little is known about tumor-microenvironment interactions in metastases, despite the fact that the vast majority of deaths from gastrointestinal tumors are related to distant metastases. Theerefore we have developed models to alter the metastatic microenvironment in the liver, and we analyze clinical samples from patients with liver metastases of gastrointestinal cancers. Our aim is to understand how cancer cells progress in the liver parenchyma, in order to find ways to slow down or even revert this process.

Who we are

Group members

  • Marco Gerling (PI): I am a researcher and principle investigator in Rune Toftgård's laboratory at the Department of Biosciences and Nutrition at Karolinska Institutet and a clinician in oncology at Karolinska University Hospital, Tema Cancer.
  • Agneta Andersson, Biomedical Scientist
  • Xiaoze Li-Wang, Senior Lab Manager
  • Maryam Saghafian, Senior Lab Manager (currently on maternity leave)
  • Ewa Dzwonkowska, MSc; Ewa has completed an internship with us and finished her Master’s thesis on pancreatic cancer liver metastases in close collaboration with Martin Enge’s group at KI campus Solna. The aim of her Master's project was to decipher cellular crosstalk in liver metastases using single cell sequencing. Ewa has extended her stay with us beyond the completion of her Master's.

Previous members

  • Rosan Heijboer, MSc: Rosan was a visiting student from Utrecht University in The Netherlands from March to December 2018 and set up a pancreas cancer metastases model in genetically modified mice.
  • Anna Pivitera, MSc: Anna joined as a visiting PhD student from Sicily from April to July 2019, working on bioinformatics analysis of stromal signaling modules in colorectal cancer.

Main collaboration partners in Stockholm:

Key publications relevant for ongoing projects:

Growth patterns of colorectal cancer liver metastases and their impact on prognosis: a systematic review.
Fernández Moro C, Bozóky B, Gerling M
BMJ Open Gastroenterol 2018 ;5(1):e000217

Stromal Hedgehog signalling is downregulated in colon cancer and its restoration restrains tumour growth.
Gerling M, Büller NV, Kirn LM, Joost S, Frings O, Englert B, et al
Nat Commun 2016 08;7():12321

Lgr6 labels a rare population of mammary gland progenitor cells that are able to originate luminal mammary tumours.
Blaas L, Pucci F, Messal HA, Andersson AB, Josue Ruiz E, Gerling M, et al
Nat. Cell Biol. 2016 Dec;18(12):1346-1356

Current Funding

Join the Group!

Are you interested in uncovering the role of the tumor microenvironment in tumor progression & metastasis?

Send your CV and a list of references to marco.gerling@ki.se.

Department of Biosciences and Nutrition (BioNut), H2