Journal Club: Adhesion strength of tumor cells predicts metastatic disease in vivo

by Kaykobad Hossain

Even though most tumors are local during diagnosis, a significant number of tumors can become invasive and metastasize to other organs, resulting in higher risk of mortality. Various factors affect the cancer relapse, however, there is no prognostic marker to identify the metastasizing cells and to predict the spread of cancer. In this article, researchers applied adhesion measurements of cancer cells to predict metastatic ability in a mouse model.  In addition, human patient samples were also stratified to invasive carcinoma, non-invasive ductal carcinoma and healthy reduction tissue based on adhesion strength.

To compare the adhesion strength of invading cells and primary tumour, human breast carcinoma cells exposed to lentiviral vectors (containing GFP and luciferase) were injected to fat pads of mice and tumoral and stromal GFP+ cells were collected after 6 weeks. After the cell adhesion assessment, it was found that the cells in stroma were significantly less adhesive when compared to tumour-resident cells.

Next, the researchers have sorted cancer cells to weakly adherent and strongly adherent types and injected to mice fat pads along with unsorted cells. Even though the size of the tumour did not differ based on the adhesion strength of the injected cells, 265 differentially expressed genes were identified by transcriptional analyses of primary tumours that are associated with adhesion strength. Moreover, Gene Ontology terms were identified in weakly adherent tumours, many of which are related to cell migration/locomotion.

Moreover, when it comes to tumour metastasis, higher lung metastasis was observed in mice injected with weakly adherent cells, indicating that weakly adherent cells might be the primary drivers of metastasis in mouse model.

Finally, analysis of patient samples from healthy and cancerous tissue showed that cells derived from invasive cancer tissue are associated with lower adhesion strength and non-invasive cancer cells and healthy reduction tissue have higher adhesion strength.

In short, adhesion strength can be used to predict metastasis of cancer in murine model and to stratify patient tissues into disease and non-disease subtypes.

 

Figure 2 from Kane et al. 2025: Primary tumors cluster based on adhesion phenotype of injected cells despite no difference in primary tumor size among groups

Continue your reading  here:

Kane MA, Birmingham KG, Yeoman B, Patel N, Sperinde H, Molley TG, Beri P, Tuler J, Kumar A, Klein S, Zare S, Wallace A, Katira P, Engler AJ. Adhesion strength of tumor cells predicts metastatic disease in vivo. Cell Reports 2025 Mar 25;44(3):115359. doi: 10.1016/j.celrep.2025.115359 

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