Cancers as wounds that do not heal: differences and similarities between renal regeneration/repair and renal cell carcinoma.
Cancers have been described as wounds that do not heal, suggesting that the two share common features. By comparing microarray data from a model of renal regeneration and repair (RRR) with reported gene expression in renal cell carcinoma (RCC), we asked whether those two processes do, in fact, share molecular features and regulatory mechanisms. The majority (77%) of the genes expressed in RRR and RCC were concordantly regulated, whereas only 23% were discordant (i.e., changed in opposite directions). The orchestrated processes of regeneration, involving cell proliferation and immune response, were reflected in the concordant genes. The discordant gene signature revealed processes (e.g., morphogenesis and glycolysis) and pathways (e.g., hypoxia-inducible factor and insulin-like growth factor-I) that reflect the intrinsic pathologic nature of RCC. This is the first study that compares gene expression patterns in RCC and RRR. It does so, in particular, with relation to the hypothesis that RCC resembles the wound healing processes seen in RRR. However, careful attention to the genes that are regulated in the discordant direction provides new insights into the critical differences between renal carcinogenesis and wound healing. The observations reported here provide a conceptual framework for further efforts to understand the biology and to develop more effective diagnostic biomarkers and therapeutic strategies for renal tumors and renal ischemia.
Riss
Joseph
J
Laboratory of Biosystems and Cancer, Comparative Oncology Program, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. rissjo@mail.nih.gov
Khanna
Chand
C
Koo
Seongjoon
S
Chandramouli
Gadisetti V R
GV
Yang
Howard H
HH
Hu
Ying
Y
Kleiner
David E
DE
Rosenwald
Andreas
A
Schaefer
Carl F
CF
Ben-Sasson
Shmuel A
SA
Yang
Liming
L
Powell
John
J
Kane
David W
DW
Star
Robert A
RA
Aprelikova
Olga
O
Bauer
Kristin
K
Vasselli
James R
JR
Maranchie
Jodi K
JK
Kohn
Kurt W
KW
Buetow
Ken H
KH
Linehan
W Marston
WM
Weinstein
John N
JN
Lee
Maxwell P
MP
Klausner
Richard D
RD
Barrett
J Carl
JC
D000818:Animals; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000473:pathology*; D005260:Female; D015870:Gene Expression; D007668:Kidney / Q000502:physiology*; D007680:Kidney Neoplasms / Q000235:genetics / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D012038:Regeneration / Q000235:genetics / Q000502:physiology*