Molecule Information

General Information of the Molecule (ID: Mol04327)

• Name: SPARC (SPARC) ,Homo sapiens
• Synonyms: Basement-membrane protein 40; Osteonectin; Secreted protein acidic and rich in cysteine
• Molecule Type: Protein
• Gene Name: SPARC
• Gene ID: 6678
• Sequence:
  MRAWIFFLLCLAGRALAAPQQEALPDETEVVEETVAEVTEVSVGANPVQVEVGEFDDGAE
  ETEEEVVAENPCQNHHCKHGKVCELDENNTPMCVCQDPTSCPAPIGEFEKVCSNDNKTF
  D SSCHFFATKCTLEGTKKGHKLHLDYIGPCKYIPPCLDSELTEFPLRMRDWLKNVLVTL
  YE RDEDNNLLTEKQKLRVKKIHENEKRLEAGDHPVELLARDFEKNYNMYIFPVHWQFGQ
  LDQ HPIDGYLSHTELAPLRAPLIPMEHCTTRFFETCDLDNDKYIALDEWAGCFGIKQKD
  IDKD LVI
• Function: Appears to regulate cell growth through interactions with theextracellular matrix and cytokines. Binds calcium and copper, severaltypes of collagen, albumin, thrombospondin, PDGF and cell membranes.There are two calcium binding sites; an acidic domain that binds 5 to 8Ca with a low affinity and an EF-hand loop that binds a Ca ionwith a high affinity.
• Uniprot ID: SPRC_HUMAN
• Ensembl ID: ENSG0000011314011
• HGNC ID: HGNC:11219

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  IDUE: Irregularity in Drug Uptake and Drug Efflux

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Lapatinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Breast adenocarcinoma [ICD-11: 2C60.1] [1]

• Sensitive Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Sensitive Drug: Lapatinib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vivo Model: Athymic nude mice model; Mus musculus
• Experiment for Molecule Alteration: CD spectroscopy assay; SDS-PAGE assay
• Experiment for Drug Resistance: Cell viability assay; Fluorescence microscope assay
• Mechanism Description: HER2-positive breast cancer constitutes 20 % of reported cases, characterized by excessive expression of HER2 receptors, pivotal in cell signaling and growth. Immunotherapy, the established treatment, often leads to multidrug resistance and tumor recurrence. There's a critical need for an effective strategy delaying drug resistance onset and ensuring cancer cell eradication. This study aimed to develop nanoparticles using human serum albumin (HSA) coupled with vitamin E (alpha-tocopherol succinate), loaded with a tyrosine kinase inhibitor (TKI) or aromatase inhibitor (AI). Nanoparticles were formed via desolvation, where HSA(VE) conjugates self-organized into a nanoparticle structure, incorporating TKI/AI either through chemical conjugation or direct binding to HSA. Physico-chemical analyses-such as infrared spectroscopy (IR), gel permeation chromatography (GPC), UV, IR, and CD spectroscopy confirmed HSA(VE) binding and drug incorporation into nanoparticles, evaluating their drug entrapment, release efficiency. Cell viability assays and in-vitro experiments on resistant and sensitive cell lines demonstrated effective drug encapsulation and absorption over time. Both in vitro and in vivo studies demonstrated that a combination of Lapa@HSA(VE) NPs and Let@HSA(VE) NPs in the ratio 75:25 inhibited tumor development and enhanced apoptosis significantly compared to individual NP treatment and free drug. The combination NPs therapy exhibited significant efficacy even in Lapa-resistant cell lines.

References

• Ref 1: Combination therapy of Lapatinib/Letrozole-based protein-vitamin nanoparticles to enhance the therapeutic effectiveness in drug-resistant breast cancer. Colloids Surf B Biointerfaces. 2025 Mar;247:114399.