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The early detection of tumor dissemination is a challenge in cancer diagnosis because
biomarkers for invasiveness are largely lacking in clinical medicine. Osteopontin is
frequently secreted by cancer cells and plays important roles in their ability to metastasize.
According to a meta-analysis, Osteopontin is signifi cantly associated with decreased patient
survival. Osteopontin levels are also markers for stage, grade, and early tumor progression,
refl ecting a common molecular underpinning for distinct clinical measures (Weber et al. Brit
J Cancer 2010;103:861). However, Osteopontin physiologically acts as an inducer cytokine
for cellular immunity, which may protect from cancer through immune surveillance. Th e
structural basis for the discrepant eff ects between tumor- and host-Osteopontin had long
not been elucidated. Because we have identifi ed the genetic basis of metastasis as aberrant
expression or splicing of stress response genes, we have studied Osteopontin splice variants in
malignant tumors. Osteopontin is subject to alternative splicing, which yields three messages,
Osteopontin-a, -b and -c. Th e shortest form, Osteopontin-c is selectively expressed in
invasive, but not in non-invasive, breast tumor cell lines, and it eff ectively supports anchorage
independence. Osteopontin-c is present in 75-80% of breast cancers and 0% of normal breast
tissues. Furthermore, Osteopontin-c detects a higher percentage of breast cancers than ER,
PR, or HER2. In particular, a fraction of triple-negative breast cancers stains positively for
Osteopontin-c (Mirza et al. Int J Cancer 122:889). Due to its absence from normal tissue,
Osteopontin-c may be a superior biomarker for cancer progression. Its measurement in blood
as a means of early detection is currently under investigation.
Georg F. Weber attended medical school in Wuerzburg, Germany. He worked at the Dana-Farber Cancer
Institute, Harvard Medical School from 1990 through 1999 and is currently on the faculty at the University of
Cincinnati. Georg F. Weber has published around 70 scientifi c reports, including many in the most respected
professional journals, and various monographs, most recently a textbook on molecular oncology. He holds
several patents. As a component of his mission to research cancer dissemination, Georg F. Weber is the
founder and chief executive offi cer of MetaMol Theranostics, a company specialized in diagnosis and treatment
of cancer metastasis.
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