Cancer cells have a different response to nutrient limitation than healthy cells; therefore, targeting nutrient acquisition pathways has potential as a therapeutic strategy for limiting cancer cell growth. In this episode, Aimee Edinger discusses a recent study from her group, which describes the effects of a sphingolipid-based compound, SH-BC-893, in multiple pre-clinical cancer models. SH-BC-893 simultaneously disrupts both glucose and amino acid transporters and was effective against both rapid- and slow-growing tumors without affecting normal tissues. The results of this study support further exploration of the therapeutic potential of this compound.
There is substantial crosstalk between tumor cells and surrounding stromal cell populations, and the specific microenvironment of a tumor greatly influences progression, malignancy, metastasis, plasticity, and therapeutic response. In this episode, Michael Stürzl, Elisabeth Naschberger, and Andrea Liebl discuss their study, which identifies endothelial cell secretion of the protein SPARCL1 as an important regulator of colorectal cancer aggressiveness. SPARCL1 expression was increased in endothelial cells from normal colon and in tumor endothelial cells that were isolated from patients with a favorable prognosis and dramatically reduced in tumor endothelial cells from patients with aggressive colorectal carcinoma. Together, the results of this study indicate that endothelial cell-derived SPARCL1 promotes an antitumorigenic microenvironment by inducing cell quiescence and limiting angiogenesis.
Ovarian cancer is difficult to diagnose at early stages, and once it has metastasized, it is associated with a very high mortality rate. During transcoelomic metastasis, ovarian tumor cells detach from the primary tumor site and migrate to the peritoneal cavity, where their survival is supported by tumor-associated macrophages (TAMs). In the accompanying video, Yale University professor Wang Min describes how TAMs are recruited to ovarian tumor cells in the peritoneal environment to form spheroids that drive the early stages of metastasis. His recent study, published this week in the JCI, has shown that tumors attract macrophages by releasing cytokines. The macrophages then secrete growth factors such as EGF that promote tumor cell adhesion and proliferation, leading to the formation of tumor cell spheroids. This work elucidates a mechanism that may be a useful therapeutic target for treating ovarian and other transcoelomic metastatic cancers.
Pulmonary hypertension (PH) refers to a collection of vascular diseases that are characterized by increased arterial pressure in the lung, which can subsequently lead to heart failure and possibly death. It is not clear how PH develops or how early events in the disease correlate with later phenotypes. In this episode, Stephen Chan discusses work from his laboratory that links increased vascular stiffness to altered glutamine metabolism in the pathogenesis of PH. The results of this study provide important insight into the development of PH and identify metabolic pathways that have potential as therapeutic targets for PH.
Alexander Rudensky’s research has defined regulatory T cells and the roles they play in autoimmunity, tolerance, allergies, infections, and cancer. After completing his PhD in Moscow in the early 1980s, Rudensky moved to the United States to study T cells under the mentorship of Charles Janeway. He is currently a professor of immunology at the Memorial Sloan Kettering Cancer Center. JCI Editor at Large Ushma Neill interviews Dr. Rudensky about his childhood in the Soviet Union and his early interest in mathematics and science. He discusses the mentors and coworkers who have shaped his research interests over time, and speculates about the immunological discoveries we can expect in years to come.