MMP

M. W. Roomi, A. Niedzwiecki, M. Rath

Journal of Cellular Medicine and Natural Health, Oct 2018

Despite sporadic progress, cancer has thus far eluded preventive and therapeutic approaches that can lead to an effective control of this global epidemic. The single most important reason for this failure is the fact that no effective intervention became available to impede the pathological pathways common to all types of cancer. In our study, we targeted metalloproteinases (MMPS), endopeptidases that are involved in the breakdown of extracellular matrix (ECM). Among them, MMP-2 and MMP-9 are critically involved in all stages of cancer development including tumor growth, invasion and metastasis.

Roomi MW, Bhanap B, Niedzwiecki A, Rath M.

J. Oncobiomarkers. 2015;2(1): 17

Abstract:

The matrix metalloproteinases (MMPs) are a family of zinc containing endopeptidases that degrade various components of the extra cellular matrix. Among the many types of MMPs that have been identified, MMP-2 (gelatinase A) and MMP-9 (gelatinase B) are thought to play a key role in cancer metastasis. These MMPs are able to modify tumor microenvironment by degrading type IV collagen found in the cellular basement membrane. MMP-2 and -9 are essential in facilitating cancer cell invasion, tumor progression, and metastasis, thereby shortening patient survival in all cancer types.

Roomi MW, Efremov E, Niedzwiecki A, Rath M.

WCRJ 2019; 6: e1421 DOI: 10.32113/wcrj_201911_1421 (World Cancer Research Journal)

Abstract:

Objective: The prevention and treatment of cancer remain a challenge. Current treatments are largely unsuccessful due to high toxicity. The most effective way to reduce global mortality from cancer is to block the initial stages of the disease, common to all types of cancer – invasion and metastasis. The elevated levels of ma-trix metalloproteinases, such as MMP-9 play a key role in tumorigenesis, angiogenesis, apoptosis, cancer invasion and metastasis. Among various therapeutic modalities, vaccines are the most effective and af-fordable approaches against diseases in general. In the global fight against cancer, a vaccine capable to impede MMP-2 and MMP-9 activity could open the door for effective prevention and even cure. We previously reported that mice immunized with synthetic oligopeptides containing specific amino acid sequences from human MMP-2 and MMP-9 showed a significant reduction in melanoma tumors and tumor burden. Materials and Methods: Here we tested a syngeneic approach to cancer vaccines by investigating whether immunization of mice with rodent derived MMP-9 oligopeptides would generate sufficient immune response and anticancer efficacy. Accordingly, C57Bl/6 mice were immunized with three oligopeptides containing specific sequences from rat MMP-9 and two oligopeptides from mouse MMP-9. All these peptides showed to be highly immunogenic in mice.

M.W. Roomi, T. Kalinovsky, M. Rath and A. Niedzwiecki
Dr. Rath Research Institute, 1260 Memorex Drive, Santa Clara, CA 95050
Oncology Letters 2015; 9(6), 2871-2873

Abstract:

Strong clinical and experimental evidence demonstrates association of elevated levels of matrix metalloproteinase MMP-9 with cancer progression, metastasis and shortened patient survival, as it plays a key role in tumor cell invasion and metastasis by digesting the basement membrane and ECM components. MMP-9 is secreted in both the monomeric and dimeric form. Though there is little research on MMP-9 dimers, some studies have shown the dimer to be associated with more aggressive tumor progression as cell migration depends upon MMP-9 dimer, not the monomer.