Abstract
BackgroundCancer stem cells are thought to play a pivotal role in tumor maintenance, metastasis, tumor therapy resistance and relapse. Hence, the development of methods for non-invasive in vivo detection of cancer stem cells is of great importance.Methodology/Principal FindingsHere, we describe successful in vivo detection of CD133/prominin, a cancer stem cell surface marker for a variety of tumor entities. The CD133-specific monoclonal antibody AC133.1 was used for quantitative fluorescence-based optical imaging of mouse xenograft models based on isogenic pairs of CD133 positive and negative cell lines. A first set consisted of wild-type U251 glioblastoma cells, which do not express CD133, and lentivirally transduced CD133-overexpressing U251 cells. A second set made use of HCT116 colon carcinoma cells, which uniformly express CD133 at levels comparable to primary glioblastoma stem cells, and a CD133-negative HCT116 derivative. Not surprisingly, visualization and quantification of CD133 in overexpressing U251 xenografts was successful; more importantly, however, significant differences were also found in matched HCT116 xenograft pairs, despite the lower CD133 expression levels. The binding of i.v.-injected AC133.1 antibodies to CD133 positive, but not negative, tumor cells isolated from xenografts was confirmed by flow cytometry.Conclusions/SignificanceTaken together, our results show that non-invasive antibody-based in vivo imaging of tumor-associated CD133 is feasible and that CD133 antibody-based tumor targeting is efficient. This should facilitate developing clinically applicable cancer stem cell imaging methods and CD133 antibody-based therapeutics.
Highlights
Many malignant tumors contain a subset of so-called cancer stem cells (CSCs) with features similar to those of normal stem cells
We present here results on the specific accumulation of a fluorescently labeled associated CD133 (AC133).1 monoclonal antibody (mAb) in CD133/prominin. Prominin-1 (CD133)-positive xenograft tumors detected by non-invasive in vivo fluorescence imaging
These data provide the first evidence that non-invasive in vivo imaging of tumor-associated CD133 (AC133), a well-known CSCmarker, is feasible. Relative to their negative counterparts, substantially higher amounts of injected antibody were found on both CD133overexpressing U251 and HCT116 wild-type cells, the latter expressing CD133 at endogenous levels similar to those of primary CD133+ glioblastoma stem-like cells
Summary
Many malignant tumors contain a subset of so-called cancer stem cells (CSCs) with features similar to those of normal stem cells. The frequencies of CSCs are found to vary from less than 1 to more than 25% of the cells in a tumor [1,2,3] Cardinal features of these stem-like cells are long-term self-renewal, tumorigenicity upon xenotransplantation to immunocompromised mice, and a certain differentiation capacity. There is growing evidence that CSCs drive metastasis [1,4,5]. They seem to be highly resistant to chemotherapy and radiation and may be crucial in tumor recurrence after conventional therapy. Cancer stem cells are thought to play a pivotal role in tumor maintenance, metastasis, tumor therapy resistance and relapse. The development of methods for non-invasive in vivo detection of cancer stem cells is of great importance
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