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ÀÎÅױ׸° ¥á3¥â1Àº CCN2 ¹ßÇö ¹× ÇǺΠÁ¾¾ç Çü¼ºÀ» ÃËÁøÇÏ´Â Áٱ⼼Æ÷ ¿¬±¸
ÀÎÅױ׸° ¥á3¥â1Àº CCN2 ¹ßÇö ¹× ÇǺΠÁ¾¾ç Çü¼ºÀ» ÃËÁøÇÏ´Â Áٱ⼼Æ÷ ¿¬±¸
  • ÀúÀÚVeronika Ramovs, Ana Krotenberg Garcia, Ji-Ying Song, Iris de Rink, Maaike Kreft, Roel Go
  • ÃâÆÇ»ç¾ÆÁø
  • ÃâÆÇÀÏ2020-07-12
  • µî·ÏÀÏ2020-12-21
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Epidermal-specific deletion of integrin ¥á3¥â1 almost completely prevents the formation of
papillomas during 7,12-Dimethylbenz [a]anthracene/12-O-tetradecanoylphorbol-13-acetate
(DMBA/TPA) two-stage skin carcinogenesis. This dramatic decrease in tumorigenesis was
thought to be due to an egress and premature differentiation of ¥á3¥â1-depleted hair bulge
(HB) stem cells (SCs), previously considered to be the cancer cells-of-origin in the DMBA/
TPA model. Using a reporter mouse line with inducible deletion of ¥á3¥â1 in HBs, we show
that HB SCs remain confined to their niche regardless of the presence of ¥á3¥â1 and are
largely absent fromskin tumors. However, tumor formation was significantly decreased in
mice deficient for ¥á3¥â1 in HB SCs. RNA sequencing of HB SCs isolated from short-term
DMBA/TPA?treated skin showed ¥á3¥â1- dependent expression of the matricellular protein
connective tissue growth factor (CCN2), which was confirmed in vitro, where CCN2
promoted colony formation and 3D growth of transformed keratinocytes. Together, these
findings show that HBs contribute to skin tumorigenesis in an ¥á3¥â1-dependent manner
and suggest a role of HB SCs in creating a permissive environment for tumor growth
through the modulation of CCN2 secretion.

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6. Ä¡·á¹ý(Therapeutical Method) 22

Á¦ 2Æí ¿¬±¸³í¹®
Integrin ¥á3¥â1 in hair bulge stem cells modulates CCN2
expression and promotes skin tumorigenesis

1. Introduction 23
2. Results 24
3. Discussion 29
4. Materials and Methods 33
5. Animal experiments 34
6. Cell culture 35
7. Data Availability 36
8. References 36

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