{"id":50039,"date":"2017-02-20T00:00:00","date_gmt":"2017-02-19T23:00:00","guid":{"rendered":"http:\/\/www.pcb.ub.edu\/how-tumor-cells-hijack-healthy-cells-to-promote-metastasis\/"},"modified":"2020-11-18T15:11:51","modified_gmt":"2020-11-18T14:11:51","slug":"how-tumor-cells-hijack-healthy-cells-to-promote-metastasis","status":"publish","type":"post","link":"https:\/\/www.pcb.ub.edu\/en\/how-tumor-cells-hijack-healthy-cells-to-promote-metastasis\/","title":{"rendered":"How tumor cells hijack healthy cells to promote metastasis"},"content":{"rendered":"

Metastasis, responsible for the majority of deaths in patients with cancer, is the process by which cancer cells separate from the original tumor to form new tumors in other organs or tissues of the body. Although initially some types of carcinoma have a very limited ability to invade the tissue around them, they finally find the mechanism to do so, thus increasing the aggressiveness of the cancer.<\/p>\n

\nFibroblasts at the service of tumor invasion<\/strong><\/p>\n

The victims of this \u2018kidnapping\u2019 are fibroblasts, a cell type that is responsible for the synthesis and organization of the extracellular matrix. \u201cFibroblasts are professionals in maintaining healthy tissues, and are able to create tunnels in the tissues to travel through,\u201d says Anna Labernadie (right, with Trepat), Juan de la Cierva postdoc at IBEC and first author of the study. \u201cThey use this ability to restore the tissues when we suffer an injury.\u201d<\/p>\n

The researchers discovered that cancer cells use the mobility of fibroblasts to escape the tumor and travel through tissues. The surrounding tumor, or stroma, modifies these fibroblasts and uses them for the invasion. From this point, the fibroblasts turn \u2018bad\u2019 and start to serve the cancerous cells, tracing paths for them through the extracellular matrix surrounding the tumor.<\/p>\n

Although this tumor-host interaction had already been described, the IBEC researchers have now shown that fibroblasts not only create tunnels beyond the stroma, but exert physical forces to drag cancer cells through these tunnels, promoting the direct invasion of healthy tissue. \u201cIt\u2019s like a train: the fibroblasts are locomotives and the cancer cells are wagons,\u201d says Labernadie. Through measuring the cellular forces using techniques that they developed and patented themselves, the IBEC group has demonstrated for the first time how fibroblasts drag off the cancer cells to promote tumor metastasis.<\/p>\n

\nUnity is strength<\/strong><\/p>\n

The main challenge of the study was to identify the mechanism by which cancer cells adhere to fibroblasts and move together. This turned out to be a a biophysical interaction between two different proteins, one located on the surface of cancer cells called E-cadherin, and another expressed on the surface of fibroblasts, called N-cadherin. \u201cThese proteins are the nanoscale hooks that enable cells to join together,\u201d says Trepat. \u201cUntil now, we knew very little about this interaction.\u201d<\/p>\n

Despite the different natures of the two proteins, the study reveals that the join between cancer cells and fibroblasts is just as strong as that which connects cancer cells, which emphasizes that this unusual interaction is much more effective than previously thought. \u201cIt\u2019s not the first time that we\u2019ve seen a functional junction between two different cell types, but we were surprised at the efficiency of these atypical unions as transmitters of force for cancer invasion,\u201d says Trepat, who\u2019s also a researcher at the Faculty of Medicine of the University of Barcelona and the Centre for Biomedical Research Network in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN<\/a>).<\/p>\n

\nPartnership with\u00a0Ferrer and\u00a0Mind the Byte<\/strong><\/p>\n

The researchers used cells and tissues obtained from patients with lung and skin cancer. \u201cWe identified this mechanism in very different tumors, which suggests that it may be universal,\u201d stresses Trepat. \u201cBecause of the poor prognosis for patients who have suffered cancer metastasis, identifying the mechanisms that promote tumor growth can help us find ways to stop it.\u201d<\/p>\n

That the interaction has been specifically identified in cancer makes it a very attractive therapeutic target. The group headed by Trepat has already\u00a0created a partnership with pharmaceutical company Ferrer and biotech firm Mind the Byte<\/a>\u00a0to design inhibitors of this interaction. \u201cThe problem for many cancer therapies is that they not only eliminate tumor cells, but also healthy ones,\u201d says Trepat. \u201cWe\u2019re working on developing molecules that inhibit the progression of the tumor without affecting the physiological behavior of other cells.\u201d<\/p>\n

This research was developed by IBEC\u2019s Integrative Cell and Tissue Dynamics group led by Xavier Trepat in collaboration with the group of\u00a0Erik Sahai at the Francis Crick Institute in London. The project received funding from several sources, including MEIC (formerly MINECO), the Generalitat of Catalonia, the European Research Council, the Obra Social \u201cla Caixa\u201d, Marie Sklodowska-Curie Actions, EMBO fellowships, FP7, the Fundaci\u00f3 La Marat\u00f3 de TV3 and an AXA Research grant.
\n\u00a0<\/p>\n

\u2022Reference article:<\/strong>\u00a0A. Labernadie, T. Kato, A. Brugu\u00e9s, X. Serra-Picamal, S. Derzsi, E. Arwert, A. Weston, V. Gonz\u00e1lez-Tarrag\u00f3, A. Elosegui-Artola, L. Albertazzi, J. Alcaraz, P. Roca-Cusachs, Erik Sahai, X. Trepat (2017). \u201cA mechanically active heterotypic E-cadherin\/N-cadherin adhesion enables fibroblasts to drive cancer cell invasion<\/a>\u201d.\u00a0Nature Cell Biology, e-pub ahead of print.<\/p>\n","protected":false},"excerpt":{"rendered":"

A team of researchers\u00a0led by Xavier Trepat \u2013ICREA research professor at the Institute for Bioengineering of Catalonia (IBEC)<\/a>\u00a0based at PCB\u2013\u00a0has identified a mechanism by which cancer cells manage to escape the tumor to promote metastasis. The study, which was published today and will be on the cover of the prestigious journal\u00a0Nature Cell Biology (doi:10.1038\/ncb3478<\/a>),\u00a0and has been supported by the\u00a0Obra Social \u201cla Caixa\u201d<\/a>, revealed that tumor cells can reprogramme their healthy neighbours, dragging them out of the tumor and into other tissues.<\/p>\n

\u00a0<\/p>\n","protected":false},"author":1,"featured_media":55109,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"inline_featured_image":false,"footnotes":""},"categories":[8],"tags":[],"class_list":["post-50039","post","type-post","status-publish","format-standard","has-post-thumbnail","category-uncategorized"],"acf":[],"yoast_head":"\nHow tumor cells hijack healthy cells to promote metastasis - Parc Cient\u00edfic de Barcelona<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.pcb.ub.edu\/en\/how-tumor-cells-hijack-healthy-cells-to-promote-metastasis\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"How tumor cells hijack healthy cells to promote metastasis - Parc Cient\u00edfic de Barcelona\" \/>\n<meta property=\"og:description\" content=\"A team of researchers\u00a0led by Xavier Trepat \u2013ICREA research professor at the Institute for Bioengineering of Catalonia (IBEC)\u00a0based at PCB\u2013\u00a0has identified a mechanism by which cancer cells manage to escape the tumor to promote metastasis. 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