A journey to uncharted territory: new technical frontiers in studying tumor–stromal cell interactions

Abstract

The crosstalk between tumor cells and cells of the tumor stroma dictate malignant progression and represent an intriguing and viable anticancer therapeutic target. The successful development of therapeutics targeting tumor-stroma interactions is tied to the insight provided by basic research on such crosstalk. Tumor-stroma interactions can be transient and dynamic, and they occur within defined spatiotemporal contexts among genetically and compositionally heterogeneous populations of cells, yet methods currently applied to study the said crosstalk do not sufficiently address these features. Emerging imaging and genetic methods, however, can overcome limitations of traditional approaches and provide unprecedented insight into tumor-stroma crosstalk with unparalleled accuracy. The comprehensive data obtained by applying emerging methods will require processing and analysis by multidisciplinary teams, but the efforts will ultimately rejuvenate hope in developing novel therapies against pro-tumorigenic tumor-stroma crosstalk.

High levels of EGFR expression in tumor stroma are associated with aggressive clinical features in epithelial ovarian cancer

“…The tumor stroma is increasingly perceived as a major contributor to the pathogenesis and disease progression in practically all cancer types. 10 …”

Characterization of the Tumor Microenvironment and Tumor–Stroma Interaction by Non-invasive Preclinical Imaging

“…Additionally, immune cells and adipocytes may further impact the metabolic tumor phenotype ( 334 ). Closer to the in vivo scenario, ex vivo tumor/stroma immunostaining, molecular profiling from tissue microarrays of excised tumors ( 338 ), or multiplexed staining and in situ transcriptome profiling techniques ( 339 ) improve further our understanding of tumor–stroma interaction. For example, Choi et al ( 338 ) classified breast cancer subtypes of patient tumors into four subgroups defined by the ex vivo expression of the glycolysis markers Glut-1 and/or CA-IX in the tumor and stroma, respectively: Warburg type (tumor: GLUT-1 and/or CA-IX positive; stroma: Glut-1 and CAIX negative), reverse Warburg type (tumor: Glut-1 and CAIX negative; stroma: GLUT-1 and/or CA-IX positive), mixed type (tumor and stroma: GLUT-1 and/or CA-IX positive), and null type (tumor and stroma: Glut-1 and CAIX negative).…”

Parenchyma–stromal interactions induce fibrosis by secreting CCN2 and promote osteoclastogenesis by stimulating RANKL and CD68 through activated TGF‐β/BMP4 in ameloblastoma

“…Solid tumors are composed of parenchyma and stroma. The parenchyma is considered an essential component, and the stroma as its support . However, it is increasingly apparent that the stroma also provides the microenvironment necessary for molecular exchanges between these two components .…”