Year: 2021

The main group of enzymes responsible for the collagen and other protein degradation in extracellular matrix (ECM) are matrix metalloproteinases (MMPs) [1]. Matrix metalloproteinases (MMPs) are a large family of calcium-dependent zinc-containing endopeptidases, which are responsible for the tissue remodeling and degradation of the extracellular matrix (ECM), including collagens, elastins, gelatin, matrix glycoproteins, and proteoglycan [2]. MMP family can be divided into six groups: collagenases, gelatinases, stromelysins, matrilysins, membrane-type MMPs, and other non-classified MMPs [3]. The MMPs are involved in many biologic processes, such as, tissue repair and remodulation, cellular differentiation, embryogenesis, morphogenesis , cell mobility, angiogenesis, cell proliferation and migration, wound healing, apoptosis. The deregulation of MMPs activity leads to development of numerous diseases [1, 4].

 

Available Antibodies for Matrix Metalloproteinases (MMPs)

 

Target	Cat.No.	Product Name	Applications	Reactivity
MT1-MMP	AB-A3713	MT1-MMP Rabbit mAb	WB	Human,Mouse,Rat
MMP1	AB-A1191	MMP1 Rabbit pAb	WB	Human
MMP2	AB-A19080	MMP2 Rabbit mAb	WB	Human,Mouse,Rat
MMP2	AB-A6247	MMP2 Rabbit pAb	WB, IHC	Human,Mouse,Rat
MMP3	AB-A11418	MMP3 Rabbit mAb	WB, IHC	Human,Mouse,Rat
MMP3	AB-A1202	MMP3 Rabbit pAb	WB, IF	Human,Mouse,Rat
MMP7	AB-A0695	MMP7 Rabbit pAb	WB	Human,Rat
MMP8	AB-A1963	MMP8 Rabbit pAb	WB, IF	Human,Mouse,Rat
MMP9	AB-A2095	[KO Validated] MMP9 Rabbit pAb	WB, IF	Human,Mouse,Rat
MMP9	AB-A0289	MMP9 Rabbit pAb	WB, IHC, IF	Human,Mouse,Rat
MMP10	AB-A3033	MMP10 Rabbit pAb	WB, IHC, IF	Human,Mouse,Rat
MMP11	AB-A11088	MMP11 Rabbit mAb	WB	Human,Mouse,Rat
MMP12	AB-A11017	MMP12 Rabbit mAb	WB, IHC	Human,Mouse
MMP12	AB-A1709	MMP12 Rabbit pAb	WB, IHC, IF	Human,Mouse,Rat
MMP13	AB-A11148	MMP13 Rabbit mAb	WB, IHC, IF	Human
MMP13	AB-A1606	MMP13 Rabbit pAb	WB	Human,Mouse
MMP16	AB-A10409	MMP16 Rabbit pAb	WB, IHC, IF	Human,Mouse,Rat
MMP17	AB-A3030	MMP17 Rabbit pAb	WB, IHC	Human,Mouse,Rat
MMP25	AB-A15886	MMP25 Rabbit pAb	WB, IHC, IF	Human,Mouse,Rat

 

References

1. J Cell Physiol. 2016 Dec;231(12):2599-621.

2. Bioorg Med Chem. 2007 Mar 15;15(6):2223-68.

3. J Enzyme Inhib Med Chem. 2016;31(sup1):177-183.

4. Cells. 2020 May; 9(5): 1076.

 

Among the multiple immune cells, macrophages plays an important role throughout the tumor progression process. They are converted into tumor-associated macrophages (TAMs) when they are recruited into the tumor microenvironment. Induced by different microenvironmental signals, macrophages would polarize into two functional phenotypes, classically activated macrophages (M1) and alternatively activated macrophages (M2). M2 macrophages are often further subdivided into M2a, M2b, M2c, and M2d based on phenotypic variations.

As a promising targets for tumor therapy, more and more researches are focusing on TAMs.

The functional biomarkers of TAMs are often used to evaluate or define the subpopulations of TAMs. According to a large number of experimental studies, TAMs biomarkers can be approximately classified into the following types: Cell surface markers, Transcription factors, Cytokines & Chemokines, Growth factors, Metabolic enzymes, Extracellular matrix (ECM) components.

Types of biomarkers	Potential biomarkers
Cell surface markers	CD206, CD163, TGFβ receptor, CD40, CD80, CD86
Transcription factors	STAT1, STAT3, STAT6, IRF3 ,IRF4, IRF5, IRF7
Cytokines & Chemokines	TNFα, IL1β, IL12, IL10, ALOX15, CCL18, CCL2, CCL5, CCL7,CXCL8, CXCL12, M-CSF
Growth factors	EGF, VEGF, PDGF, FGF, TGFβ
Metabolic enzymes	iNOS, Arginase 1
ECM components	MMP‐9

 

Representative Antibodies for Biomarkers of Tumor-associated macrophages

 

Biomarker	Cat.No.	Product Name	Applications	Cross-reactivity
iNOS	AB-A0312	iNOS Rabbit pAb	WB, IHC	Human, Mouse, Rat
Arginase 1	AB-A4923	Arginase 1 (ARG1) Rabbit mAb	WB, IHC, IF	Human, Mouse, Rat
STAT1	AB-AP0054	Phospho-STAT1-Y701 Rabbit mAb	WB	Human, Mouse, Rat
STAT3	AB-AP0705	Phospho-STAT3-Y705 Rabbit mAb	WB, IP	Human, Mouse

 

Representative ELISA Kits for Biomarkers of Cancer-associated macrophages

 

Biomarker	Cat.No.	Product Name	Sensitivity	Assay Range
IL-1β	AB-RK00001	Human IL-1 beta ELISA Kit	3.21 pg/mL	6.25-400 pg/ml
IL12	AB-RK00014	Human IL-12 p70 ELISA Kit	8.56 pg/mL	31.2-2000pg/ml
TNFα	AB-RK00030	Human Tumor Necrosis Factor Alpha ELISA Kit	6.12 pg/mL	15.6-1000 pg/ml
IL-10	AB-RK00012	Human IL-10 ELISA Kit	6.15 pg/mL	31.2-2000pg/ml
CCL2	AB-RK00052	Human Monocyte Chemotactic Protein 1 ELISA Kit	9.12pg/mL	31.2-2000pg/ml
CCL5	AB-RK00077	Human CCL5/Rantes ELISA Kit	11.24 pg/mL	31.2-2000pg/ml

 

 

Extracellular Vesicles and particles (EVPs), including exosomes, are membrane-bound cargos (size range 30–150 nm) comprised of a lipid bilayer that contain various biomolecules, such as proteins or nucleic acids, and play crucial roles in different cellular or pathological processes. With increasing recognition of the central role of exosomes in intercellular (cell-to-cell) communication and transportation, current exosome research covers almost all research areas in biomedical science (immunology, neuroscience, oncology, endocrinology, and cardiovascular research) and have the great potential in both diagnosis (some of contained proteins or nucleic acids in exosomes can serve as biomarkers of diseases) and therapy (engineered exosomes can serve as new drug delivery system with high efficiency and low risks). Based on one latest study published on Cell (Hoshino et al., 2020, Cell 182, 1-18. https://doi.org/10.1016/j.cell.2020.07.009) , tens of new pan-EVP markers and tumor-derived EVP markers in human tissues and plasma EVP proteins have been identified and can be useful for cancer detection and cancer type determination. This study greatly move the clinical application of exosomes forward in cancer diagnosis.

 

Based on this study, we collected representative EVP proteins or genes that are proposed to be pan-exosome markers or potential cancer biomarkers as below and provided featured antibodies for exosome research.

 

Traditional pan-exosome markers	HSPA8/Hsc70, HSP90AA1/Hsp90α, HSP90AB1/Hsp90β, HSPA4/Hsp70, CD9, TSG101, ALIX, CD63, CD81, FLOT1, FLOT2
Additional pan-exosome markers	ACTB, RAP1B, Moesin, fibronectin 1, A2M, Gelsolin, B2M, PRDX2, Filamin A
Pan-tumor exosome markers	THBS2, VCAN, DNAJA1, CRMP2, PGK1, EHD2, CAVIN1, FGGY, CD36
PaCa plasma EVP markers	CA2, CD55, KRAS, PEBP1, SRI, TGM2, PSMA4, XPNPEP2, ABCB11, ALPL, ABCB1
LuCa plasma EVP markers	CFB, CD53, PRSS1, RDX, Radixin, CHMP4B, PSMB1, ACTA2, Histone H2A.Z
Neuroblastoma plasma EVP markers	FTH1, KRT17, H3F3A, CD14, EPB42, KRT8
Osteosarcoma plasma EVP markers	ACTA1, CD10/MME

Tumor microenvironment (TME) consists of a complex network of tumor cells, infiltrating and resident host cells (immune and inflammatory cell, fibroblasts and myofibroblasts,etc), the blood and lymphatic vascular network,extracellular matrix (ECM), secreted factors(cytokines, chemokines,etc), the metabolites and microvesicles (exosomes,etc).

 

Hypoxia and Angiogensis represent an important cellular player in the tumor microenvironment. Cancer cells are frequently surrounded by hypoxic microenvironment and, to survive, they have evolved multiple adaptations. One of the hallmark adaptations for cancer cells is the rewired metabolism, which is so-called tumor metabolic reprogramming, resulting in neoangiogenesis, metastasis, and immune evasion. Several hypoxia-responsive molecular determinants, such as hypoxia-inducible factors (HIFs), guide the cellular adaptation to hypoxia by gene activation. HIFs promotes vessel growth by upregulating multiple pro-angiogenic factors such as growth factors, cytokines, chemokines and ECM remodeling MMPs that mediate key aspects of endothelial, stromal, and vascular support cell biology.

 

Summary: top research targets of Hypoxia and Angiogensis

 

The hypoxia-inducible factor (HIF) family : HIF-1α, HIF-1β,HIF-2α

Growth factors：VEGF, bFGF, PDGF, EGF, TGF-β,HGF, IGF-1,etc

Chemokines：SDF-1, CXCL12, IL-8,etc

Regulators of angiogenesis：Angiopoietin-1, -2, EPO, Endothelin-1, tPA, thrombospondin-1, VWF,etc

Receptors：VEGFRs, FGFR, PDGFR, Tie-1,-2, Eph, Integrins, Notch,etc

Signal regulating kinases：AKT, ERK, p38, JNK, FAK,etc

Nitric oxide synthase：eNOS, iNOS

Metalloproteinase：MMP1, MMP2, MMP-3, MMP-7, MMP-9, MT1-MMP,etc

Oxidoreductases：HO-1, NOXs, COX-2,etc

Endothelial cell markers：PECAM-1/CD31

Vascular permeability markers：VE-Cadherin

 

Representative Antibodies

[KO Validated] HIF1α Rabbit pAb (AB-A16873)

HIF1β/ARNT Rabbit mAb (AB-A19532)

MMP2 Rabbit pAb (AB-A6247)

MMP3 Rabbit mAb (AB-A11418)

MMP7 Rabbit pAb (AB-A0695)

MMP9 Rabbit pAb (AB-A0289)

Heme Oxygenase 1 (HO-1/HMOX1) Rabbit mAb (AB-A19062)

CD31/PECAM1 Rabbit mAb (AB-A19014)

CD31/PECAM1 Rabbit mAb (AB-A20228)

 

Representative ELISA Kits

 

Representative Products for Growth Factors
Target Name	CatalogNo	Product Name	Assay Range
VEGFA	AB-RK00023	Human VEGFA ELISA Kit	31.2-2000pg/ml
	AB-RK00028	Mouse VEGFA ELISA Kit	15.6-1000pg/ml
	AB-RK00066	Rat VEGFA ELISA Kit	15.6-1000 pg/ml
	AB-RK00567	Canine Vascular Endothelial Growth Factor A ELISA Kit (VEGFA)	15.6-1000 pg/mL
	AB-RK02493	Human Vascular Endothelial Growth Factor 121 ELISA Kit (VEGF121)	15.6-1000 pg/mL
	AB-RK02494	Human Vascular Endothelial Growth Factor 165 ELISA Kit (VEGF165)	15.6-1000 pg/mL
	AB-RK03274	Mouse Vascular Endothelial Growth Factor 121 ELISA Kit (VEGF121)	15.6-1000 pg/mL
	AB-RK03382	Porcine Vascular Endothelial Growth Factor A ELISA Kit (VEGFA)	15.62-1000 pg/mL
VEGFB	AB-RK06286	Bovine Vascular endothelial growth factor B (VEGFB) ELISA Kit	31.2-2000pg/mL
VEGFC	AB-RK02496	Human Vascular Endothelial Growth Factor C ELISA Kit (VEGFC)	78-5,000 pg/mL
	AB-RK03276	Mouse Vascular Endothelial Growth Factor C ELISA Kit (VEGFC)	15.6-1000 pg/mL
EGF	AB-RK00024	Human EGF ELISA Kit	1.56-100 pg/ml
	AB-RK00024HS	Human EGF ELISA Kit (High Sensitivity)	1.56-100 pg/ml
	AB-RK00197	Rat EGF ELISA Kit	15.6-1000 pg/mL
	AB-RK00364	Mouse EGF ELISA Kit	3.9-250pg/ml
	AB-RK03317	Porcine Epidermal Growth Factor ELISA Kit (EGF)	15.6-1000 pg/mL
	AB-RK06984	Dog Pro-epidermal growth factor (EGF) ELISA Kit	31.2-2000pg/mL
	AB-RK06985	Pig Pro-epidermal growth factor (EGF) ELISA Kit	15.6-1000pg/mL
TGFβ1	AB-RK00055	Human TGF-beta 1 ELISA Kit	31.2-2000 pg/ml
	AB-RK00057	Mouse TGF-beta 1 ELISA Kit	7.8-500 pg/mL
	AB-RK00059	Rat Transforming Growth Factor Beta 1 ELISA Kit (TGFb1)	31.2-2000pg/ml
	AB-RK00755	Guinea pig Transforming Growth Factor Beta 1 ELISA Kit (TGFb1)	15.6-1000 pg/mL
	AB-RK00771	Horse Transforming Growth Factor Beta 1 ELISA Kit (TGFb1)	78-5000 pg/mL
	AB-RK06255	Chicken TGF beta-1 proprotein (TGFB1) ELISA Kit	31.2-2000pg/mL
HGF	AB-RK03404	Rabbit Hepatocyte Growth Factor ELISA Kit (HGF)	15.6-1000 pg/mL
	AB-RK06117	Bovine Hepatocyte growth factor (HGF) ELISA Kit	0.156-10ng/mL
	AB-RK09321	Rat Hepatocyte Growth Factor ELISA Kit (HGF)	31.2-2000pg/mL
Representative Products for Chemokines
Target Name	CatalogNo	Product Name	Assay Range
CXCL12	AB-RK00140	Human SDF-1 alpha ELISA Kit	125-8000 pg/mL
	AB-RK00168	Mouse CXCL12/SDF-1 ELISA Kit	46.8-3000pg/ml
	AB-RK02255	Human Stromal Cell Derived Factor 1 ELISA Kit (SDF1)	0.156-10 ng/ml
	AB-RK03177	Mouse Stromal Cell Derived Factor 1 ELISA Kit (SDF1)	62.5-4000 pg/mL
	AB-RK03366	Porcine Stromal Cell Derived Factor 1 ELISA Kit (SDF1)	0.156-10 ng/ml
	AB-RK03939	Rat Stromal Cell Derived Factor 1 ELISA Kit (SDF1)	15.6-1000 pg/mL
Representative Products for Metalloproteinase
Target Name	CatalogNo	Product Name	Assay Range
MMP1	AB-RK00340	Human Total MMP-1 ELISA Kit	156-10000 pg/mL
	AB-RK00765	Horse Matrix Metalloproteinase 1 ELISA Kit (MMP1)	0.312-20 ng/ml
	AB-RK03354	Porcine Matrix Metalloproteinase 3 ELISA Kit (MMP3)	4.69-300 ng/ml
	AB-RK04041	Sheep Matrix Metalloproteinase 1 ELISA Kit (MMP1)	0.312-20 ng/ml
	AB-RK06196	Bovine Interstitial collagenase (MMP1) ELISA Kit	0.156-10ng/mL
	AB-RK06197	Pig Interstitial collagenase (MMP1) ELISA Kit	0.156-10ng/mL
	AB-RK09325	Rat Matrix Metalloproteinase 1 ELISA Kit (MMP1)	15.6-1000pg/mL
MMP2	AB-RK00309	Human Matrix Metalloproteinase 2 ELISA Kit (MMP2)	0.625-40 ng/ml
	AB-RK03353	Porcine Matrix Metalloproteinase 2 ELISA Kit (MMP2)	31.2-2000 pg/mL
	AB-RK06200	Chicken 72 kDa type IV collagenase (MMP2) ELISA Kit	0.312-20ng/mL
MMP3	AB-RK00767	Horse Matrix Metalloproteinase 3 ELISA Kit (MMP3)	31.25-2000 pg/mL
	AB-RK01869	Human Matrix Metalloproteinase 3 ELISA Kit (MMP3)	31.2-2000 pg/mL
	AB-RK06201	Mouse Stromelysin-1 (Mmp3) ELISA Kit	78-5000pg/mL
MMP7	AB-RK00492	Bovine Matrix Metalloproteinase 7 ELISA Kit (MMP7)	15.6-1000 pg/mL
	AB-RK01870	Human Matrix Metalloproteinase 7 ELISA Kit (MMP7)	0.156-10 ng/ml
	AB-RK09314	Mouse Matrix Metalloproteinase 7 ELISA Kit (MMP7)	78-5000pg/mL

 

 

 

Featured Ferroptosis Research Tools from ABclonal

A new form of cell death, ferroptosis, was recently discovered. Ferroptosis is an iron-dependent programmed cell death resulting from alterations of metabolic processes and accumulation of lipid peroxidation that is toxic and damaging to the membrane structure. Ferroptosis initiation and execution lies at the intersection of amino acid, lipid, and iron metabolism, but ferroptosis sensitivity is also modulated by several lines of mechanisms, including A) the regulation of GSH and redox homeostasis, such as function of system Xc-, GPX4 regulation, FSP1-CoQ10- NAD(P)H pathway, sulfur transfer pathway, mevalonate (MVA) pathway, glutamine metabolic pathway, NRF2 and p53 regulatory axis; B) the regulation of iron homeostasis, such as the regulation of ATG5-ATG7-NCOA4 pathway, IREB regulation system, and the regulatory pathways of heatshock proteins; C) related enzymes around glucose and lipid metabolism, such as PHGDH, G6PD, ACSL4, and LPCAT3, etc. ; D) mitochondria function regulation, such as VDAC, mitochondrial electron transport chain (ETC) , TCA cycle and glutaminolysis.

Here, we recommend ABclonal featured antibody products against key targets of iron homeostasis and redox regulation, including,

• AB-A5865 TFRC Rabbit pAb
• AB-A11241 Ferritin Light Chain mAb
• AB-A19062 Heme Oxygenase 1 Rabbit mAb
• AB-A5695 [KO Validated] NCOA4 Rabbit pAb
• AB-A11243 GPX4 Rabbit mAb
• AB-A11159 NRF2 Rabbit pAb
• AB-A19586 NQO1 Rabbit mAb
• AB-A12768 PEBP1 Rabbit mAb
• AB-A4252 CD26 Rabbit mAb
• AB-A19701 NOX2/CYBB/gp91phox Rabbit mAb