| Added by | Cavailles |
|---|---|
| Group name | EquipeVC |
| Item Type | Journal Article |
| Title | Metastatic colorectal cancer cells maintain the TGF? program and use TGFBI to fuel angiogenesis |
| Creator | Chiavarina et al. |
| Author | Barbara Chiavarina |
| Author | Brunella Costanza |
| Author | Roberto Ronca |
| Author | Arnaud Blomme |
| Author | Sara Rezzola |
| Author | Paola Chiodelli |
| Author | Ambre Giguelay |
| Author | Guillame Belthier |
| Author | Gilles Doumont |
| Author | Gaetan Van Simaeys |
| Author | Simon Lacroix |
| Author | Takehiko Yokobori |
| Author | Bilguun Erkhem-Ochir |
| Author | Patrick Balaguer |
| Author | Eric Fabbrizio |
| Author | Emmanuel Di Valentin |
| Author | Olivier Detry |
| Author | Guy Jerusalem |
| Author | Serge Goldman |
| Author | Philippe Delvenne |
| Author | Akeila Bellahcène |
| Author | Julie Pannequin |
| Author | Vincent Castronovo |
| Author | Andrei Turtoi |
| Abstract | Colorectal cancer (CRC) cells are traditionally considered unresponsive to TGF? due to mutations in the receptors and/or downstream signaling molecules. TGF? influences CRC cells only indirectly via stromal cells, such as cancer-associated fibroblasts. However, CRC cell ability to directly respond to TGF? currently remains unexplored. This represents a missed opportunity for diagnostic and therapeutic interventions. Methods: We examined whether cancer cells from primary CRC and liver metastases respond to TGF? by inducing TGF?-induced protein ig-h3 (TGFBI) expression, and the contribution of canonical and non-canonical TGF? signaling pathways to this effect. We then investigated in vitro and in vivo TGFBI impact on metastasis formation and angiogenesis. Using patient serum samples and an orthotopic mouse model of CRC liver metastases we assessed the diagnostic/tumor targeting value of novel antibodies against TGFBI. Results: Metastatic CRC cells, such as circulating tumor cells, directly respond to TGF?. These cells were characterized by the absence of TGF? receptor mutations and the frequent presence of p53 mutations. The pro-tumorigenic program orchestrated by TGF? in CRC cells was mediated through TGFBI, the expression of which was positively regulated by non-canonical TGF? signaling cascades. TGFBI inhibition was sufficient to significantly reduce liver metastasis formation in vivo. Moreover, TGFBI pro-tumorigenic function was linked to its ability to stimulate angiogenesis. TGFBI levels were higher in serum samples from untreated patients with CRC than in patients who were receiving chemotherapy. A radiolabeled anti-TGFBI antibody selectively targeted metastatic lesions in vivo, underscoring its diagnostic and therapeutic potential. Conclusions: TGF? signaling in CRC cells directly contributes to their metastatic potential and stromal cell-independence. Proteins downstream of activated TGF?, such as TGFBI, represent novel diagnostic and therapeutic targets for more specific anti-metastatic therapies. |
| Publication | Theranostics |
| Volume | 11 |
| Issue | 4 |
| Pages | 1626-1640 |
| Date | 2021 |
| Journal Abbr | Theranostics |
| Language | eng |
| DOI | 10.7150/thno.51507 |
| ISSN | 1838-7640 |
| Library Catalog | PubMed |
| Extra | PMID: 33408771 PMCID: PMC7778592 |
| Tags | alternative TGF? signaling, Animals, Apoptosis, Biomarkers, Tumor, Cell Movement, Cell Proliferation, Colorectal Neoplasms, endothelial cells, Extracellular Matrix Proteins, Gene Expression Regulation, Neoplastic, Humans, Liver Neoplasms, Mice, Neovascularization, Pathologic, original, Prognosis, Signal Transduction, Transforming Growth Factor beta, Tumor Cells, Cultured, Xenograft Model Antitumor Assays |
| Date Added | 2021/04/21 - 09:45:51 |
| Date Modified | 2021/09/01 - 17:25:33 |
| Notes and Attachments | PubMed entry (Attachment) PubMed entry (Attachment) PubMed entry (Attachment) Texte intégral (Attachment) Texte intégral (Attachment) Texte intégral (Attachment) |
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