Enhanced growth of tumors in SPARC null mice is associated with changes in the ECM.
SPARC, a 32-kDa glycoprotein, participates in the regulation of morphogenesis and cellular differentiation through its modulation of cell-matrix interactions. Major functions defined for SPARC in vitro are de-adhesion and antiproliferation. In vivo, SPARC is restricted in its expression to remodeling tissues, including pathologies such as cancer. However, the function of endogenous SPARC in tumor growth and progression is not known. Here, we report that implanted tumors grew more rapidly in mice lacking SPARC. We observed that tumors grown in SPARC null mice showed alterations in the production and organization of ECM components and a decrease in the infiltration of macrophages. However, there was no change in the levels of angiogenic growth factors in comparison to tumors grown in wild-type mice, although there was a statistically significant difference in total vascular area. Whereas SPARC did inhibit the growth of tumor cells in vitro, it did not have a demonstrable effect on the proliferation or apoptosis of tumor cells in vivo. These data indicate that host-derived SPARC is important for the appropriate organization of the ECM in response to implanted tumors and highlight the importance of the ECM in regulating tumor growth.
Brekken
Rolf A
RA
Department of Vascular Biology, The Hope Heart Institute, Seattle, Washington 98104-2046, USA.
Puolakkainen
Pauli
P
Graves
David C
DC
Workman
Gail
G
Lubkin
Sharon R
SR
Sage
E Helene
EH
D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D002455:Cell Division; D004247:DNA / Q000235:genetics; D005109:Extracellular Matrix / Q000378:metabolism* / Q000473:pathology*; D015870:Gene Expression; D008264:Macrophages / Q000473:pathology / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D015676:Osteonectin / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
D015676:Osteonectin; D012333:RNA, Messenger; D004247:DNA