A role for ADAM12 in breast tumor progression and stromal cell apoptosis.

TY - JOUR

T1 - A role for ADAM12 in breast tumor progression and stromal cell apoptosis.

AU - Kveiborg, Marie

AU - Frohlich, Camilla

AU - Albrechtsen, Reidar

AU - Tischler, Verena

AU - Dietrich, Nikolaj

AU - Holck, Peter

AU - Kronqvist, Pauliina

AU - Rank, Fritz

AU - Mercurio, Arthur M

AU - Wewer, Ulla M.

N1 - Keywords: 3T3-L1 Cells; ADAM Proteins; Animals; Apoptosis; Breast; Breast Neoplasms; CHO Cells; Cell Growth Processes; Cricetinae; Disease Progression; Humans; Membrane Proteins; Metalloendopeptidases; Mice; Mice, Transgenic; Stromal Cells

PY - 2005

Y1 - 2005

N2 - As in developmental and regenerative processes, cell survival is of fundamental importance in cancer. Thus, a tremendous effort has been devoted to dissecting the molecular mechanisms involved in understanding the resistance of tumor cells to programmed cell death. Recently, the importance of stromal fibroblasts in tumor initiation and progression has been elucidated. Here, we show that stromal cell apoptosis occurs in human breast carcinoma but is only rarely seen in nonmalignant breast lesions. Furthermore, we show that ADAM12, a disintegrin and metalloprotease up-regulated in human breast cancer, accelerates tumor progression in a mouse breast cancer model. ADAM12 does not influence tumor cell proliferation but rather confers both decreased tumor cell apoptosis and increased stromal cell apoptosis. This dual role of ADAM12 in governing cell survival is underscored by the finding that ADAM12 increases the apoptotic sensitivity of nonneoplastic cells in vitro while rendering tumor cells more resistant to apoptosis. Together, these results show that the ability of ADAM12 to influence apoptosis may contribute to tumor progression.

AB - As in developmental and regenerative processes, cell survival is of fundamental importance in cancer. Thus, a tremendous effort has been devoted to dissecting the molecular mechanisms involved in understanding the resistance of tumor cells to programmed cell death. Recently, the importance of stromal fibroblasts in tumor initiation and progression has been elucidated. Here, we show that stromal cell apoptosis occurs in human breast carcinoma but is only rarely seen in nonmalignant breast lesions. Furthermore, we show that ADAM12, a disintegrin and metalloprotease up-regulated in human breast cancer, accelerates tumor progression in a mouse breast cancer model. ADAM12 does not influence tumor cell proliferation but rather confers both decreased tumor cell apoptosis and increased stromal cell apoptosis. This dual role of ADAM12 in governing cell survival is underscored by the finding that ADAM12 increases the apoptotic sensitivity of nonneoplastic cells in vitro while rendering tumor cells more resistant to apoptosis. Together, these results show that the ability of ADAM12 to influence apoptosis may contribute to tumor progression.

U2 - 10.1158/0008-5472.CAN-05-0262

DO - 10.1158/0008-5472.CAN-05-0262

M3 - Journal article

C2 - 15930294

SN - 0008-5472

VL - 65

SP - 4754

EP - 4761

JO - Cancer Research

JF - Cancer Research

IS - 11

ER -