The age-related increase in cancer incidence has been taken as a proof of the mutation accumulation theory of cancer in humans. Recent data suggest that longliving stem cells are the most likely target for oncogenic mutations. Nevertheless, a plenty of data point out for a major role of stromal cell in cancer growth. These data suggest that the study of the interaction between aged stromal cells and cancer initiating cells (i.e. cancer stem cells) may be of primary importance to better understand cancer biology.In this investigation we employed human mammospheres (MS) from normal and tumor tissues as a model for normal and cancer stem/progenitor cells of the mammary gland. We here report that, compared to fibroblasts from young individuals, fibroblasts from aged people and nonagenarians show an enhanced capacity to induce invasive behaviour of normal and tumor MS. Similarly, we show that in vitro senescent fibroblasts induce invasiveness of MS at a higher extent than non senescent cells. We also provide details about the molecular pathway involved in such a phenomenon, by showing that the capacity of aged/senescent fibroblasts to enhance the invasive behaviour of stem/progenitor cells is pivoted by p66Shc gene. These data support the notion that in vivo/in vitro aged stromal cells create a pro-tumorigenic environment for stem/progenitor cells of the mammary gland.
IN VIVO/IN VITRO AGED FIBROBLASTS TRIGGER MALIGNANT FEATURES IN NORMAL AND CANCER STEM/PROGENITOR CELLS OF THE MAMMARY GLAND
STORCI, GIANLUCA;TAVOLARI, SIMONA;GUARNIERI, TIZIANA;TAFFURELLI, MARIO;CECCARELLI, CLAUDIO;SANTINI, DONATELLA;Pasquale Chieco;
2007
Abstract
The age-related increase in cancer incidence has been taken as a proof of the mutation accumulation theory of cancer in humans. Recent data suggest that longliving stem cells are the most likely target for oncogenic mutations. Nevertheless, a plenty of data point out for a major role of stromal cell in cancer growth. These data suggest that the study of the interaction between aged stromal cells and cancer initiating cells (i.e. cancer stem cells) may be of primary importance to better understand cancer biology.In this investigation we employed human mammospheres (MS) from normal and tumor tissues as a model for normal and cancer stem/progenitor cells of the mammary gland. We here report that, compared to fibroblasts from young individuals, fibroblasts from aged people and nonagenarians show an enhanced capacity to induce invasive behaviour of normal and tumor MS. Similarly, we show that in vitro senescent fibroblasts induce invasiveness of MS at a higher extent than non senescent cells. We also provide details about the molecular pathway involved in such a phenomenon, by showing that the capacity of aged/senescent fibroblasts to enhance the invasive behaviour of stem/progenitor cells is pivoted by p66Shc gene. These data support the notion that in vivo/in vitro aged stromal cells create a pro-tumorigenic environment for stem/progenitor cells of the mammary gland.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
