CD24+ cells fuel rapid tumor growth and display high metastatic capacity

Abstract

IntroductionBreast tumors are comprised of distinct cancer cell populations which differ in their tumorigenic and metastatic capacity. Characterization of cell surface markers enables investigators to distinguish between cancer stem cells and their counterparts. CD24 is a well-known cell surface marker for mammary epithelial cells isolation, recently it was suggested as a potential prognostic marker in a wide variety of malignancies. Here, we demonstrate that CD24+ cells create intra-tumor heterogeneity, and display highly metastatic properties.MethodsThe mammary carcinoma Mvt1 cells were sorted into CD24− and CD24+ cells. Both subsets were morphologically and phenotypically characterized, and tumorigenic capacity was assessed via orthotopic inoculation of each subset into the mammary fat pad of wild-type and MKR mice. The metastatic capacity of each subset was determined with the tail vein metastasis assay. The role of CD24 in tumorigenesis was further examined with shRNA technology. GFP-labeled cells were monitored in vivo for differentiation. The genetic profile of each subset was analyzed using RNA sequencing.ResultsCD24+ cells displayed a more spindle-like cytoplasm. The cells formed mammospheres in high efficiency and CD24+ tumors displayed rapid growth in both WT and MKR mice, and were more metastatic than CD24- cells. Interestingly, CD24-KD in CD24+ cells had no effect both in vitro and in vivo on the various parameters studied. Moreover, CD24+ cells gave rise in vivo to the CD24− that comprised the bulk of the tumor. RNA-seq analysis revealed enrichment of genes and pathways of the extracellular matrix in the CD24+ cells.ConclusionCD24+ cells account for heterogeneity in mammary tumors. CD24 expression at early stages of the cancer process is an indication of a highly invasive tumor. However, CD24 is not a suitable therapeutic target; instead we suggest here new potential targets accounting for early differentiated cancer cells tumorigenic capacity.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-015-0589-9) contains supplementary material, which is available to authorized users.

Ribosome display and selection of single‐chain variable fragments effectively inhibit growth and progression of microspheres in vitro and in vivo

“…Screening antibody molecules that take into account stem‐like cells and cancer cells should be one of the directions for future research on immunity . Thus, our screening methods were not only based on the affinity to the microspheres but also dependent on the selective effect on their early differentiated cells . This approach ensured that subsequent identification and treatment was effective both for the microspheres and cancer cells (Figure ).…”

“…18 However, CD24 + cells are considered more closely related to the early, highly invasive, and differentiated cells in mammary tumors. 17,19 We infer that CSCs themselves may always be in a dynamic balance and inhomogeneous collective state. As Reya et al 20 have suggested, cancer cells, stem cells, and CSCs may share a common signaling pathway.…”

“…As we know, the CD44 + CD24 −/low lineage of breast cancer cells has been thought to be breast CSCs . However, CD24 + cells are considered more closely related to the early, highly invasive, and differentiated cells in mammary tumors . We infer that CSCs themselves may always be in a dynamic balance and inhomogeneous collective state.…”

Modern Biochemistry in Research of Human Malignant Cells and Experimental Oncology

“…In particular, Gay et al (2016) [42] analyzed and summarized in their review more than 30 publications concerning cellular heterogeneity of various malignant tumors (kidney, lung, colon, mammary gland, prostate, ovary, etc.). The genetic, epigenetic, and phenotypic mechanisms of intra-tumor cell heterogeneity have been described [42,46,47] . Traditionally tumor cell heterogeneity was explained with a clonal selection and adaptation models.…”

“…For example, Moghbeli et al (2014) [52] introduced different protocols used to isolate CSCs from solid tumors of colon, esophagus, liver, breast, brain, and cervix. The isolation of CSCs can be accomplished by selection of tumor cell subpopulations based on expression of one or more of cell surface markers associated with cancer self-renewal such as: CD133, CD166, CD44, CD24, beta1 integrin-CD29 and others [47,53] . The alternative hypothesis suggested that tumor growth could be mediated, at least in part, by the coalescence of multiple tumorigenic foci within a tissue, a process that would contribute to tumor heterogeneity [40,46,[54][55][56] .…”