Abstract.Integrins are transmembrane glycoproteins that consist of an α and a β subunit. Specific integrin heterodimers preferentially bind to distinct extracellular matrix (ECM) proteins to affect the characteristics of cells or the components of the ECM. Among the different integrins, β1 and β3 integrins serve essential roles in the progression of different cancer-associated processes, including the initiation, proliferation, survival, migration and invasion. Furthermore, previous studies have revealed a ratio between these two integrins in cancer cells, which also demonstrated that the functions of these two integrins are paradoxical. This indicated that the proliferation and metastasis of cancer cells are not always parallel and may be considered independently maintained. Additionally, the present review may assist in understanding certain aspects of cancer, and in making clinical decisions in a novel and more comprehensive manner. IntroductionIntegrins are transmembrane glycoproteins that consist of an α subunit and a β subunit. A total of eight different β subunits may dimerize, in limited combinations, with 18α subunits to form ≥24 distinct integrins (1,2). Specific integrin heterodimers preferentially bind to distinct extracellular matrix (ECM) proteins. Integrins may bind the ligands in ECM directly, including fibronectin and laminin, to affect the characteristics of cells or the components of ECM. Regarding cancer cells, integrins serve roles in numerous aspects, including proliferation, survival, migration and invasion (1).Integrins primarily affect cells in two ways, the first is through binding with proteins directly, including talin, vinculin and filamin, which may regulate the actin cytoskeleton of cells (3). The other is by phosphorylating the relative kinases, including focal adhesion kinases (FAKs), proto-oncogene tyrosine-protein kinase (Src)-family kinases (SFKs) and integrin-linked kinase (ILK), to activate or cooperate with the other cell signaling pathways (1,4). Additionally, integrin clustering on the cell surface and trafficking from the endosomes may affect the ligand affinity and quantity of the protein on cell surface (5-7).Among the different integrins, β1 and β3 integrins serve essential roles in the progression of different types of cancer (1,2). Furthermore, previous studies investigating the association between these two integrins have demonstrated many different perspectives (8-11), together providing a novel and more comprehensive understanding of cancer. Functions of β1 integrin in cancerIn tumors, the β1 subunit of integrin may combine with different α subunits, including α4, α5 and α2, to affect the characteristics of cancer cells, and the progression of tumors (1). The primary function of β1 integrin is to form focal adhesion between cancer cells and ECM. This adhesion is the basis for the survival of cancer cells and is also associated with their migratory and metastatic capabilities (2). There are series of proteins in the cytoplasm, including talin, kindlin and ILK, ...

Purpose: This study was to assess a gastrin-releasing peptide receptor (GRPR) and integrin αvβ3 dual targeting tracer 68Ga-BBN-RGD for positron emission tomography (PET)/computed tomography (CT) imaging of breast cancer and metastasis. Materials and Methods: Twenty-two female patients were recruited either with suspected breast cancer on screening mammography (n = 16) or underwent breast cancer radical mastectomy (n = 6). All the 22 patients underwent PET/CT at 30-45 min after intravenous injection of 68Ga-BBN-RGD. Eleven out of 22 patients also accepted 68Ga-BBN PET/CT within 2 weeks for comparison. A final diagnosis was made based on the histopathologic examination of surgical excision or biopsy. Results: Both the primary cancer and metastases showed positive 68Ga-BBN-RGD accumulation. The T/B ratios of 68Ga-BBN-RGD accumulation were 2.10 to 9.44 in primary cancer and 1.10 to 3.71 in axillary lymph node metastasis, 3.80 to 10.7 in distant lymph nodes, 2.70 to 5.35 in lung metastasis and 3.17 to 22.8 in bone metastasis, respectively. For primary lesions, the SUVmax from 68Ga-BBN-RGD PET in ER positive group was higher than that in ER negative group (P < 0.01). For both primary and metastatic lesions, SUVmean quantified from 68Ga-BBN-RGD PET correlated well with both GRPR expression and integrin αvβ3 expression. Conclusion: This study demonstrated significant uptake of a new type of dual integrin αvβ3 and GRPR targeting radiotracer in both the primary lesion and the metastases of breast cancer. 68Ga-BBN-RGD PET/CT may be of great value in discerning both primary breast cancers, axillary lymph node metastasis and distant metastases.

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