American Association for Cancer Research
00085472can130085-sup-supp_figures_s1-s2.pdf (521.09 kB)

Supplementary Figures S1-S2 from Bone Marrow–Derived CD11b+Jagged2+ Cells Promote Epithelial-to-Mesenchymal Transition and Metastasization in Colorectal Cancer

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journal contribution
posted on 2023-03-30, 21:50 authored by Francisco Caiado, Tânia Carvalho, Isadora Rosa, Leonor Remédio, Ana Costa, João Matos, Beate Heissig, Hideo Yagita, Koichi Hattori, João Pereira da Silva, Paulo Fidalgo, António Dias Pereira, Sérgio Dias

PDF file - 521K, Jagged-2 expression in human cells/tissues (S1); CRC tumor diameters do not correlate with tumor or circulating CD11b+ Jag2+ cell numbers (S2)



Timely detection of colorectal cancer metastases may permit improvements in their clinical management. Here, we investigated a putative role for bone marrow–derived cells in the induction of epithelial-to-mesenchymal transition (EMT) as a marker for onset of metastasis. In ectopic and orthotopic mouse models of colorectal cancer, bone marrow–derived CD11b(Itgam)+Jagged2 (Jag2)+ cells infiltrated primary tumors and surrounded tumor cells that exhibited diminished expression of E-cadherin and increased expression of vimentin, 2 hallmarks of EMT. In vitro coculture experiments showed that the bone marrow–derived CD11b+Jag2+ cells induced EMT through a Notch-dependent pathway. Using neutralizing antibodies, we imposed a blockade on CD11b+ cells' recruitment to tumors, which decreased the tumor-infiltrating CD11b+Jag2+ cell population of interest, decreasing tumor growth, restoring E-cadherin expression, and delaying EMT. In support of these results, we found that peripheral blood levels of CD11b+Jag2+ cells in mouse models of colorectal cancer and in a cohort of untreated patients with colorectal cancer were indicative of metastatic disease. In patients with colorectal cancer, the presence of circulating CD11b+Jag2+ cells was accompanied by loss of E-cadherin in the corresponding patient tumors. Taken together, our results show that bone marrow–derived CD11b+Jag2+ cells, which infiltrate primary colorectal tumors, are sufficient to induce EMT in tumor cells, thereby triggering onset of metastasis. Furthermore, they argue that quantifying circulating CD11b+Jag2+ cells in patients may offer an indicator of colorectal cancer progression to metastatic levels of the disease. Cancer Res; 73(14); 4233–46. ©2013 AACR.