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TIMP‐2: A Novel Biologic Therapy for Triple Negative Breast Cancer
Author(s) -
Castro Nadia Pereira,
Chowdhury Ananda,
Jensen Sandra Mae,
Cuttitta Frank,
StetlerStevenson William George,
Solomon David
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.698.2
Subject(s) - triple negative breast cancer , angiogenesis , mammary tumor , breast cancer , cancer research , metastasis , medicine , cancer , tumor progression , matrix metalloproteinase inhibitor , primary tumor , matrix metalloproteinase
Triple‐negative breast cancer (TNBC) presents the poorest prognosis among the breast cancer subtypes, having no current standardized therapy. Here, we used an orthotopic mouse model that establishes spontaneous lung metastasis from JygMC(A) cells. These primary tumors resemble human TNBC both phenotypically and molecularly. Tissue inhibitor of metalloproteinase‐2 (TIMP‐2) belongs to a small family of low molecular weight proteins identified as endogenous metalloproteinase inhibitors. These proteins modulate growth, migration and invasion of tumor cells and inhibit tumor angiogenesis. The mechanisms involve both metalloproteinase‐dependent (inhibition of protease activity) and ‐independent activities. In our TNBC model, JygMC(A) cells were implanted into both sides of the 4 th inguinal mammary fat pads of athymic nude mice (10 mice per experimental group). Ten days following tumor cell inoculation, a daily intraperitoneal (IP) injection of recombinant TIMP‐2 protein was given at doses ranging from 0.75/100ml to 6.0 mg/100ml. Tumor growth was measured biweekly by caliper measurement for a total of 4 weeks). In our TNBC model, preliminary results showed that recombinant TIMP‐2 protein inhibited tumor growth by 50% at day 34 post tumor cell injection at a dose concentration as low as 1.5 mg/100 ml. Taken together, our data show that recombinant TIMP‐2 contributes to reduction of mammary tumor size in this mouse model revealing a therapeutic potential of a biologic protein able to decrease mammary carcinoma progression. Further studies will examine the MMP‐dependent and MMP‐independent mechanisms responsible for reduced tumor growth in this model system. Moreover, these findings may lead to a more efficient clinical treatment strategy for TNBC. Support or Funding Information This work was funded by the NCI Center for Cancer Research Intramural Research Program Grant # ZIA SC009179‐24.