Discovery of the Cytocapsular Membrane as Hallmark of Malignant Tumors.

While optimizing cancer cell growth conditions, we discovered that cancer stem cells can generate second membranes outside the plasma membranes forming compartments separated from the extracellular matrix. The encapsulating membranes can extend and generate long cytocapsular tubes, wherein multiple cells can migrate. SILAC proteomics of the second cytocapsular membranes identified 400 membrane proteins, and a small subset of them are highly upregulated in cytocapsular cancers compared to normal tissues. The ATP-dependent calcium pump PMCA2 is one of the highest upregulated factors of the cytocapsular membrane, and antibodies serve as biomarkers for malignant tumors, as checked for 293 subtypes of cancers. Cytocapsular tumors have not been described before, possibly because the CC membranes do not exhibit epitopes targeted by conventional methods, and no efforts have been made to search for new cancer specific organelles. Antibodies against PMCA2 can now be used to map cancer evolution pathways in human bodies by comparisons of more than 12 000 annotated specimens from tissue banks worldwide. The current research reveals that the native malignant cancer cell is enclosed in a cytocapsular membrane. With the PMCA2 cancer biomarker available, the development of human cancers can be studied from cancer tissue banks and clinical cancer biopsies with a previously unknown diversity. The emerging knowledge on cancer-driving biomarkers opens doors for new routes in cancer diagnosis, surgery, therapy, and treatments.